AddCisplatinToGem+NabPaclitaxel2017

Cisplatin Added to Gemcitabine / Nab-Paclitaxel
Everyone,
In my post immediately above I failed to say that one does not have to be a clinical trial
participant in order to receive the 3-drug Cisplatin/Gemcitabine/Nab-Paclitaxel regimen, since
the agents are readily available off-trial.
Assuming that the disease has not progressed on a Gemcitabine regimen, all the
patient needs is a willing oncologist skilled in managing related adverse events – and the
regimen protocol, which is described in the trial record and at the end of this doc file:
/> />This may not be an approved regimen, so insurance may not cover it, although a
clever provider may be able to manage the coverage.
The regimen appears to aid those affected by BRCA mutations (which is many
pancreatic cancer victims)
PhilipJax
For “Advanced” & Metastatic Patients
Everyone,
Two items:
1. ASCO has released its guidelines for treating metastatic disease. It is not so significant as
the NCCN guidelines. So, study both, which are available here:
/> />2. Published today: the results of a small (so less reliable) study of 24 “advanced” patients
show good performance when cisplatin is added to standard gemcitabine/nab-paclitaxel. 17
of 24 patients (71%) experienced tumor-size reductions of at least 30%. Two had complete
responses, which is a very desirable and rare event. And, median overall survival was 16.5
months. See
/>There are several ongoing clinical trials which utilize the 3-drugs. See
>> Stage 4, non-randomized: />>> Stage 3 or 4, non-randomized: />>> “Advanced” and Stage 4, non-randomized: />>> Resectable & potentially-resectable: />>> Resectable & potentially-resectable: />Usually, in non-randomized studies all patients get the experimental agents. Also, be
cautions about trials which include immuno agents. On occasion, some have accelerated the
disease greatly. See
/>doc
In the last trial NCT01726582 the principal investigator is Douglas B. Evans, M.D.,
FACS, who may be the same highly-skilled surgical oncologist who once served at MD
Anderson.

PhilipJax


Response Rates Improved With
Platinum Added to NabPaclitaxel/Gemcitabine in
Advanced Pancreatic Cancer
Wayne Kuznar | Thursday, Feb 16, 2017 | />Clinical trial information: NCT01893801
The addition of a platinum agent to standard gemcitabine and nab-paclitaxel was found to be
associated with impressive response and overall survival (OS) rates in patients with stage IV
pancreatic cancer, according to findings of a small pilot trial presented at the 2017
Gastrointestinal Cancers Symposium.1
With 11 of 25 patients [44%] in the study still alive, the median OS is 16.5 months, said Gayle
Jameson, MSN, ACNP-BC, AOCN, when presenting the findings at the meeting. “We have
not seen that in stage IV pancreatic cancer to date. It’s a very small study though,” she said.
“The median survival will continue [to increase] because the data are not mature and we still
have 11 patients alive.”
The genomes of patients with metastatic pancreatic cancer contain myriad intrachromosomal
aberrations, indicating a high prevalence of DNA repair deficiencies. In the phase II Stand Up
2 Cancer trial, every patient with pancreatic ductal adenocarcinoma had multiple interstitial
copy number aberrations,2 noted Jameson, nurse practitioner and associate investigator of
Clinical Trials, HonorHealth Research Institute, Scottsdale Healthcare Research Institute.
“These types of tumors are very sensitive to platinums, which are DNA-damaging agents,”
she said.
Twenty-five patients with stage IV adenocarcinoma of the pancreas, no prior chemotherapy
for systemic disease, Karnofsky performance status (KPS) ≥70%; life expectancy ≥12 weeks,
and measurable disease were enrolled at 3 US sites between December 2013 and July 2016.
Nab-paclitaxel was administered at 125 mg/m2 undiluted, gemcitabine at 1000 mg/m2, each
infused over 30 minutes on days 1 and 8 of a 21-day cycle. In addition, patients received
either 25 mg/m2 of cisplatin infused over 60 minutes, escalated to 50 mg/m2, after the nabpaclitaxel infusion.
Median age of the patients was 65 years, all had KPS ≥80%, and 79% had an elevated

CA19-9 at baseline. Primary tumor location was the head of the pancreas in 24%, body in
32%, and tail in 24%. Twenty percent had their tumor resected.
The maximum tolerated and phase II dose of cisplatin was 25 mg/m 2. “It’s a very low dose of
cisplatin, but adding that we’ve seen a very impressive response rate,” she said.


The overall response rate (ORR) by RECIST v1.1 criteria was 71%, with 2 complete
responses (8.3%) and 15 partial responses (62.5%). The 71% ORR is “exceptional in stage
IV pancreas disease,” Jameson indicated. Most patients who had an abnormal level of CA199 at baseline had values decline by 50% to 100% within 90 days.
Eighteen of the 25 patients [72%] had a ≥30% reduction in tumor size from baseline, and 3 of
the 25 had a resolution of measurable tumor by RECIST criteria. The median survival to date
of 16.5 months “has not been seen in stage IV pancreatic cancer,” she said. Some 64% of
patients were alive at 12 months, 20% were alive at 24 months, 4% were still alive at 36
months, with 11 of the 25 patients still alive at last follow-up.
The most common drug-related grade ≥3 adverse events were thrombocytopenia (76% total;
grade 3, 36%; grade 4, 40%) with no serious bleeding events, anemia in 32% (all grade 3),
neutropenia in 24% (grade 3, 20%; grade 4, 4%), infection in 20% (grade 3, 16%; grade 4,
4%), and grade 3 diarrhea in 16%. “We’d like to expand the study but we also have a tissue
analysis that’s upcoming,” said Jameson. “As we look for genomic signatures of response,
this is going to be key.” A study examining this triplet in the neoadjuvant setting is also
planned.

References
1. Jameson GS, Borazanci E, Babiker HM, et al. A phase Ib/II pilot trial with nab-paclitaxel
plus gemcitabine plus cisplatin in patients (pts) with stage IV pancreatic cancer. Presented
at: 2017 Gastrointestinal Cancers Symposium; January 19-21, 2017; San Francisco, CA.
Abstract 341.
2. Barrett MT, Lenkiewicz, Evers L, et al. Abstract 3697: phase II study of therapy selected
by molecular profiling in patients with previously treated metastatic pancreatic cancer –
SU2C-001. Cancer Res. 2012;72(8 suppl):abstr 3697. doi:10.1158/1538-7445.AM20123697.

A phase Ib/II pilot trial with nabpaclitaxel plus gemcitabine plus cisplatin
in patients (pts) with stage IV pancreatic
cancer
Subcategory: Multidisciplinary Treatment
Category: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Meeting: 2017 Gastrointestinal Cancers Symposium
Session Type and Session Title: Poster Session B: Cancers of the Pancreas, Small Bowel
and Hepatobiliary Tract
Abstract Number: 341
Poster Board Number: Poster Session B Board #F11


Citation: J Clin Oncol 35, 2017 (suppl 4S; abstract 341)
Author(s):
Gayle S. Jameson, Erkut Hasan Borazanci, Hani M. Babiker, Elizabeth Poplin, Anna A.
Niewiarowska, Michael S. Gordon, Michael T Barrett, Karen Ansaldo, Leticia Lebron, Amy C.
Stoll, Adam Rosenthal, Lynn R. Shemanski, Ronald Lee Korn, Ramesh K. Ramanathan,
Daniel D. Von Hoff;
HonorHealth/TGen, Scottsdale, AZ; University of Arizona Cancer Center, Tucson, AZ;
Cancer Institute of New Jersey, New Brunswick, NJ; Vita Medical Associates, Fountain Hill,
PA; Pinnacle Oncology Hematology/Honor Health Research Institute, Scottsdale, AZ;
Mayo Clinic Cancer Center, Scottsdale, AZ; HonorHealth, Scottsdale, AZ;
Cancer Research And Biostatistics, Seattle, WA;
Cancer Research and Biostatistics, Seattle, WA; Scottsdale Medical Imaging, Ltd.,
Scottsdale, AZ;
Translational Genomics Research Institute (TGen) and HonorHealth, Phoenix and
Scottsdale, AZ
Abstract:
Background: Genomes of metastatic pancreatic cancers frequently contain

intrachromosomal aberrations indicating DNA repair abnormalities associated with sensitivity
to DNA damaging agents such as the platinums. Cisplatin was added to a nab-paclitaxel +
gemcitabine regimen, which has been determined to improve survival over gemcitabine alone
(NEJM 2013; 369:1691-1703). The objectives are to determine the efficacy and safety of nabpaclitaxel and gemcitabine plus cisplatin in patients with Stage IV pancreatic cancer.
Methods: Eligibility criteria included Stage IV adenocarcinoma of the pancreas, no prior
chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable
disease. Doses are nab-paclitaxel 125 mg/m2 undiluted, gemcitabine 1000 mg/m2 in 500 ml of
normal saline (NS), each infused over 30 minutes on days 1 and 8 of a 21 day cycle, along
with 3 different dose levels of cisplatin (25, 37.5 or 50 mg/m 2) in 500 ml of NS infused over 60
minutes, after the nab-paclitaxel infusion. Pre and post cisplatin hydration was given. The
maximum tolerated dose and phase II dose of cisplatin is 25 mg/m 2.
Results: 25 pts were treated; 24 were evaluable (baseline and ≥ 1 follow up CT scan). The
most common drug related grade (gr) 3 - 4 adverse events (AEs), n = 25, were
thrombocytopenia 76% (gr 3 = 36%, gr 4 = 40%) with no serious bleeding events, anemia
32% (gr 3 = 32%, gr 4 = 0%), neutropenia 24% (gr 3 = 20%, gr 4 = 4%), infection 20% (gr 3 =
16%, gr 4 = 4%), and diarrhea 16% (gr 3 = 16%, gr 4 = 0%). Peripheral neuropathy ≥ gr 3
was seen in only 1 pt (gr 3 = 4%). Grade 5 AEs were infection (1), cardiac arrest (1), and
stroke (1). Median time on therapy was 5.5 months, range (1 – 9.5).
By RECIST 1.1 criteria, 2 pts had complete response (8.3%), 15 partial response (62.5%), 4
stable disease (16.7%), and 3 progressive disease (12.5%). Median overall survival to date
as of 11/10/16 is 16.5 months.
Conclusions: Although a small study, the high response rate and landmark evolving median
survival are very encouraging. This regimen is being expanded in patients with stage IV


pancreatic cancer, neoadjuvant and adjuvant settings. Clinical trial information:
NCT01893801

Unfolding: Gemcitabine + Abraxane +
Cisplatin for Stage 4 Pancreatic Cancer

By Pancreatica | Published February 15, 2017 />Since the mid-1990s, teams affiliated with Dr. Daniel Von Hoff have ushered in two of the
three key advances in the first-line treatment of advanced pancreatic cancer (ductal
adenocarcinoma of the pancreas). This includes seminal work from a research institute
affiliated with the University of Texas at San Antonio on the development of gemcitabine for
the treatment of pancreatic cancer, AND per published article in 2013 as acting lead of an
international consortium presenting the MPACT study results that represented a formal
introduction to the advantages of gemcitabine plus Abraxane (nab-paclitaxel) in the treatment
of metastatic pancreatic cancer. The other key advance was the 2011 article in the New
England Journal of Medicine by French researchers demonstrating the survival advantage of
the 4-drug regimen known as FOLFIRINOX over gemcitabine alone in the therapy for
advanced pancreatic cancer.
Now another treatment improvement from a new Von Hoff team that appears, at least thus
far, to offer potential further increased survival advantage. First in the April 2015 American
Association for Cancer Research (AACR) annual meeting, and later at the January 2017
Gastrointestinal Cancers Symposium (American Society of Clinical Oncology – ASCO) Von
Hoff’s team from HonorHealth Research Institute in Scottsdale, Arizona and other institutions,
including fellow researchers Gayle S. Jameson, Erkut Borazanci and other authors, have
reported out the rolling results of an ongoing Phase Ib/II clinical trial that assess the addition
of cisplatin to the original gemcitabine plus Abraxane regimen in the treatment of metastatic
pancreatic cancer (clinical trial: NCT01893801).
In the 2015 AACR meeting, the researchers published their work in a meeting abstract
entitled, “High complete and partial response rate in a phase Ib pilot trial with cisplatin plus
albumin-bound paclitaxel and gemcitabine in patients with advanced pancreatic cancer.”
Under the rationale that pancreatic cancer not infrequently demonstrates abnormalities in
DNA repair that may tend to respond to such entities as platinum salts, they added cisplatin
to the gemcitabine plus Abraxane chemotherapy regimen for patients with stage IV
pancreatic cancer. Ten patients with advanced pancreatic cancer were enrolled with two
showing a complete response, six showing a partial response, one offering stable disease,
and one demonstrating progression of their pancreatic cancer. Four patients had serious
adverse side effects including sepsis/pneumonia, bacteremia, clostridium difficile colitis, and

neutropenic fever/pneumonia. Despite the sobering events profile, the clinical results were
encouraging enough for the researchers to move forward to the stage II status of the clinical
trial.


In the 2017 Gastrointestinal Cancers Symposium, the research team both published an
abstract and presented their further results in a Poster Presentation, “A phase Ib/II pilot trial
with nab-paclitaxel plus gemcitabine plus cisplatin in patients with stage IV pancreatic
cancer.” The 25 patients in three U.S. sites met inclusion criteria including being diagnosed
with stage IV pancreatic cancer between December 2013 and July 2016. All of the patients
were treated with the three-drug regimen. 20% had their tumor resected. 18 of the 25 patients
had a greater than 30% reduction in the pancreatic cancer tumor size. The median survival to
date (at the time of presentation) was 16.5 months, with 20% alive at 24 months. 40% of the
patients experienced a grade 4 adverse effect including primarily such conditions as
thrombocytopenia, anemia, neutropenia, infection, or substantive diarrhea.
Dr. Erkut Borazanci indicated that there appears to be, “something related to ‘BRCA-ness’ in
pancreatic tumors,” referring to the positive response that patients with BRCA1 or BRCA2
genetic-mutation-related cancers tend to have to platinum drugs (and perhaps PARP
inhibitors). Please note our Pancreatica Blog on this topic Here.
These preliminary survival outcome results with the cisplatin + gemcitabine + Abraxane
regimen for advanced pancreatic cancer are remarkably encouraging, to say the least. The
adverse effects of this chemotherapy regimen though are rather profound, and would require
serious management and care. One interesting finding was the high number of patients who
became available for surgery during the course of the treatment (the authors have indicated
that a separate study of this outcome is anticipated). It is important to note that these are
meeting results with a small number of patients, and the results are not yet published in a
peer-reviewed journal. It will be highly interesting to see if the outcomes of this treatment
approach hold up in a Phase III trial, and as peer reviewed. If so, the current Von Hoff team
will have again succeeded in changing the landscape of the treatment for advanced
pancreatic cancer.

References
Proceedings: AACR 106th Annual Meeting; April 18-22, 2015; Philadelphia, PA; Cancer Res
2015;75(15 Suppl):Abstract LB-003. doi:10.1158/1538-7445.
2017 Gastrointestinal Cancers Symposium, ASCO, San Francisco; J Clin Oncol 35, 2017
(suppl 4S; abstract 341); Poster Session B Board #F11.
Dale O’Brien, MD

Phase Ib/II Study Reports High
Response Rates Seen With Addition
of Cisplatin to Regimen for
Advanced Pancreatic Cancer


By Caroline Helwick | April 10, 2016 | />An 80% response rate with traditional chemotherapy is basically unheard of [in
advanced pancreatic cancer]. But we know this is a very small sample, and we are
very cautious.
— Gayle Jameson, MSN, ACNP-BC, AOCN
The oncology research team at HonorHealth Research Institute in Scottsdale, Arizona, is
spearheading a phase Ib/II trial that is demonstrating promising results with a novel regimen
in patients with advanced pancreatic cancer. “The patients we are treating have advanced
adenocarcinoma of the pancreas, for which survival is typically very grim,” said principal
investigator of the clinical trial Gayle Jameson, MSN, ACNP-BC, AOCN.
“We have added a third drug to the two-drug combination of albumin-bound
paclitaxel/gemcitabine, which originated here at our center, and the responses we have seen
in the first 10 patients are remarkable in several ways,” she revealed. Albumin-bound
paclitaxel, or paclitaxel protein-bound particles for injectable suspension (Abraxane), was
formerly known as nab-paclitaxel.
Ms. Jameson and co-investigator Erkut Borazanci, MD, MS, described their study in an
interview with The ASCO Post.
Ms. Jameson said they are excited to share positive results in this challenging malignancy.

“We want to instill hope, not only in patients but also in physicians, nurses, and oncology
teams,” she said. “Many patients come to us for a second opinion, after their oncologist has
told them to get their affairs in order. We now have multiple options for stage IV cancer. It’s a
new ballgame, and there are choices that patients can make to potentially improve the
quantity and quality of their lives.”
Study Details and Rationale
Data available on the first 10 patients were reported at the 2015 American Association for
Cancer Research Annual Meeting.1 Based on the encouraging responses observed, the
phase II part of the study was expanded to enroll 25 patients, 20 of whom have been treated.
The trial is evaluating a regimen of albumin-bound paclitaxel/gemcitabine plus cisplatin. The
choice of cisplatin is based on the recent discovery that pancreatic cancers contain
chromosomal aberrations indicative of DNA-repair deficiencies, which are often sensitive to
DNA-damaging agents.
“Looking at the genome, we see changes that speak to the fact that there is something
related to ‘BRCA-ness’ in pancreatic tumors. The idea is that we can target these global
aberrations with DNA-damaging agents, such as cisplatin,” Dr. Borazanci explained.


This treatment requires a lot of attention. In our center, we are very responsive to the
needs of our patients. A lot of supportive care is needed around this regimen [of
cisplatin plus nab-paclitaxel/gemcitabine].
— Erkut Borazanci, MD, MS
To be eligible for the phase Ib/II study, patients must have stage IV pancreatic cancer and no
prior chemotherapy for systemic disease, a Karnofsky performance status ≥ 70, a life
expectancy ≥ 12 weeks, and measurable disease.
In phase Ib, patients received albumin-bound paclitaxel at 125 mg/m2 undiluted and
gemcitabine at 1,000 mg/m2, each infused over 30 minutes on days 1 and 8 of a 21-day
cycle. They also received cisplatin at one of three doses—25, 37.5, or 50 mg/m2—after the
albumin-bound paclitaxel infusion. In phase II, all patients will receive cisplatin at 25 mg/m2,
which was determined to be the maximum tolerated dose.

Preliminary Results
Of the 10 patients treated in phase Ib, the response rate was 80%, including 2 complete
responses (20%), 6 partial responses (60%), 1 patient with stable disease (10%) and 1
patient with progressive disease (10%). “An 80% response rate with traditional chemotherapy
is basically unheard of,” Ms. Jameson commented. “But we know this is a very small sample,
and we are very cautious. We can’t make big claims based on 10 patients, but we are very
encouraged.”
These responses occurred early, by the first staging evaluation, in seven patients. Responses
were accompanied by exponential decreases in CA19-9 in the six patients with elevated
CA19-9 at baseline. Maximal percentage change from baseline was 40% to 100% for these
six patients.
“We saw a very prompt drop in the CA-19 marker and a very rapid response by decreases in
RECIST [Response Evaluation Criteria in Solid Tumors] measurements. After three cycles, by
9 weeks, we saw markers plummet and tumors shrink, and we also saw patients feeling
better,” Ms. Jameson noted.
Some responses have been durable, she added. “One of our patients with a complete
response after 12 cycles is alive 2 years and 3 months after starting this regimen and has no
evidence of disease,” she reported. The investigators have not yet reported results for the 20
patients treated in the expanded phase but indicated they “continue to be encouraged.”
Impact of Cisplatin
The ASCO Post asked the investigators to what degree cisplatin added to the benefit seen
with standard regimens in this disease.
The phase III MPACT trial established nab-paclitaxel/gemcitabine as first-line treatment, with
a 28% reduction in mortality (P < .001) over gemcitabine alone.2 The response rate, by
independent review, was 23% with the doublet vs 7% with gemcitabine alone (P < .001).


Similarly, with FOLFIRINOX (fluorouracil/leucovorin/irinotecan/oxaliplatin), the response rate
in the pivotal French phase III trial was 31.6% in the FOLFIRINOX group vs 9.4% in the
gemcitabine group (P < .001).3 Interestingly, the addition of cisplatin to gemcitabine has not

been shown to improve survival in other previous studies.
“This goes back to the idea of building upon other successes. We know that albumin-bound
paclitaxel is synergistic with gemcitabine. Based upon genomic research in pancreas
cancer,4 we think that the addition of cisplatin may add even greater synergy,” Dr. Borazanci
said.
“I don’t want to compare this small population to those other trials, and there are certainly no
head-to-head studies, but from what we’re seeing so far, the outcomes in our study are
unique,” he said. Ms. Jameson added: “To see 8 of 10 patients do so well has been very
exciting.”
Tolerability
“Patients are tolerating the regimen well, but we have a strong focus on supportive care,” said
Ms. Jameson. The investigators expected to see more neuropathy and renal toxicity, but so
far, the toxicities have not been more than anticipated. “What we actually see is that, because
of the rapid response, some patients feel better much more quickly. Several patients who
presented with significant pain were able to completely wean off of narcotics,” Ms. Jameson
reported.
Adverse events grade ≥ 3 were observed in 60% and ≥ 4, in 30% of patients. Serious
adverse events occurred in four patients, including non-neutropenic sepsis/pneumonia, nonneutropenic bacteremia, neutropenic fever/pneumonia, and Clostridium difficile colitis.
Is Regimen Ready for the Clinic?
Ms. Jameson and Dr. Borazanci are aware that oncologists may see these results and try this
regimen on their own patients. Those doing so should be aware, said Dr. Borazanci. “This
treatment requires a lot of attention. In our center, we are very responsive to the needs of our
patients. A lot of supportive care is needed around this regimen,” he noted.
The clinicians’ biggest concerns have been the prevention of dehydration, neuropathy, and
fatigue. They use intravenous fluids liberally. “It’s not been completely smooth sailing,” he
acknowledged.

Novel Regimen for Stage IV Pancreatic Cancer
•

•
•

A phase Ib/II study of 10 patients with advanced pancreatic cancer achieved
responses in 80%, including 20% complete responses, using a regimen of albuminbound paclitaxel/gemcitabine plus cisplatin.
The use of cisplatin is based upon the finding of chromosomal aberrations that point to
DNA-repair deficiency.
The phase II study is enrolling up to 25 patients.


Ms. Jameson emphasized the need to strictly follow the clinical trial protocol. “Our concern is
that clinicians may take this regimen and modify it, which would not be advisable,” she said.
The investigators expect to have data from the phase II trial for presentation in 2017. If the
phase II results are consistent with the initial findings, they hope to move this regimen
forward.
The researchers wanted to credit their funding sources: the Seena Magowitz Foundation,
which is dedicated to pancreatic research and treatment, as well as Mattress Firm, which
collects public donations for pancreatic cancer research. Stand Up To Cancer funded basic
research associated with the project in collaboration with the Translational Genomics
Research Institute. ■
Disclosure: Ms. Jameson is on the speakers bureau for Celgene. Dr. Borazanci reported no
potential conflicts of interest.
References
1. Jameson GS, Borazanci E, Poplin E, et al: High complete and partial response rate in a
phase 1b pilot trial with cisplatin plus albumin-bound paclitaxel and gemcitabine in patients
with advanced pancreatic cancer. 2015 AACR Annual Meeting. Abstract LB-003. Presented
April 19, 2015.
2. Von Hoff DD, Ervin T, Arena FP, et al: Increased survival in pancreatic cancer with nabpaclitaxel plus gemcitabine. N Engl J Med 369:1691-1703, 2013.
3. Conroy T, Desseigne F, Ychou M, et el: FOLFIRINOX versus gemcitabine for metastatic
pancreatic cancer. N Engl J Med 364:1817-1825, 2011.

4. Ruiz C, Lenkiewicz E, Evers L, et al: Advancing a clinically relevant perspective of the
clonal nature of care. Proc Natl Acad Sci U S A 108:12054-12059, 2011.

TGen-HonorHealth study: High rate
of tumor shrinkage among
pancreatic cancer patients
Results of the Triplet Clinical Trial at HonorHealth Research Institute based on the TGen
Triple research presented at ASCO-GI symposium in San Francisco
The Translational Genomics Research Institute 25Apr2017
/>

SCOTTSDALE, Ariz. - April 25, 2017 - Adding cisplatin to the standard gemcitabine/nabpaclitaxel drug treatment provided a very high rate of tumor shrinkage for patients with
advanced pancreatic cancer, according to the results of a pilot clinical trial conducted by the
HonorHealth Research Institute and the Translational Genomics Research Institute (TGen).
These statistically significant and clinically meaningful improvements in overall response and
survival rates resulted from a phase Ib/II clinical study performed at the HonorHealth
Research Institute, a partnership of HonorHealth and TGen.
The results were presented during the 2017 Gastrointestinal Cancers Symposium, sponsored
by the American Society of Clinical Oncology, in San Francisco. Connecting a global network
of more than 40,000 cancer professionals, the society serves as the leading resource for best
practices in clinical oncology research and academic and community practices.
"After just three treatment cycles, we saw tumor markers plummet and some patients' tumors
shrink significantly in just nine weeks," said Gayle Jameson, nurse practitioner and principal
investigator of the clinical trial, who is highly encouraged by the response. "After treatment,
two patients had no evidence of disease and are alive over three years after starting this
regimen. This is very rare with traditional chemotherapy."
Dr. Daniel Von Hoff, TGen Distinguished Professor and Physician-in-Chief who devised the
clinical trial, agreed: "Although a small study, the high response rate and landmark evolving
median survival are very encouraging, and this regimen is being expanded for patients with
stage IV pancreatic cancer." Dr. Von Hoff also is chief scientific officer at the HonorHealth

Research Institute.
Of the 24 evaluable patients (those whose response to a treatment could be measured
because enough information was collected) who were enrolled in the study:
•
•
•

Eleven patients are still alive. The median overall survival rate of 16.5 months exceeds
the historical average survival of six-12 months with standard chemotherapy.
Seventeen of 24 patients -- 71 percent -- had a reduction in tumor size of at least 30
percent.
Two of those 17 patients had a complete response -- no detectable tumor.

This pilot clinical trial began in 2013 through a partnership between the HonorHealth
Research Institute and TGen. It was funded by Stand Up To Cancer, Mattress Firm, the
Arizona Diamondbacks, and the Scottsdale-based Seena Magowitz Foundation.
Symptoms of pancreatic cancer usually do not appear until the disease progresses to its late
stages, making it difficult to treat. Only about one in four patients survives more than a year
after diagnosis, and fewer than 10 percent survive more than five years. Pancreatic cancer
this year will take the lives of more than 43,000 Americans, making it the nation's thirdleading cause of cancer-related death.
The results of this trial are encouraging and deserve additional testing prior to becoming a
standard of care for patients with advanced pancreatic cancer. Through research, the


HonorHealth Research Institute and TGen aim to provide hope and a better chance for
patients to live for years instead of months.
The current standard of care for advanced pancreatic cancer -- a combination of nabpaclitaxel and gemcitabine -- was developed by TGen and the HonorHealth Research
Institute, and approved by the U.S. Food and Drug Administration in 2013.
About TGen
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit

organization dedicated to conducting groundbreaking research with life changing results.
TGen is focused on helping patients with neurological disorders, cancer, and diabetes,
through cutting edge translational research (the process of rapidly moving research towards
patient benefit). TGen physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children. Working with collaborators in
the scientific and medical communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and effectiveness of the translational
process. TGen is allied with City of Hope, a world-renowned independent research and
cancer and diabetes treatment center. This precision medicine alliance enables both institutes
to complement each other in research and patient care, with City of Hope providing a
significant clinical setting to advance scientific discoveries made by TGen. For more
information, visit: . Follow TGen on Facebook, LinkedIn and Twitter
@TGen.
Media Contact: Steve Yozwiak, TGen Senior Science Writer, 602-343-8704,

About HonorHealth
HonorHealth is a non-profit health system serving an area of 1.6 million people in the greater
Phoenix area. The network encompasses five acute-care hospitals, an extensive medical
group, outpatient surgery centers, a cancer care network, clinical research, medical
education, a foundation and community services with approximately 11,500 employees, 3,700
affiliated physicians and 3,100 volunteers. HonorHealth was formed by a merger between
Scottsdale Healthcare and John C. Lincoln Health Network. HonorHealth's mission is to
improve the health and well-being of those we serve. Learn more at HonorHealth.com.
Media Contact: Debbie Jacobson, 480-323-1384,
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases
posted to EurekAlert! by contributing institutions or for the use of any information through the
EurekAlert system.

Below is the clinical trial description.

NabPaclitaxel+Cisplatin+Gemcitabine in
Patients With Previously Untreated
Metastatic Pancreatic Ductal
Adenocarcinoma (PDA)
/>The recruitment status of this study is unknown. The completion date has passed and the
status has not been verified in more than two years.
Verified February 2014 by Pancreatic Cancer Research Team.
Recruitment status was: Recruiting
Sponsor: Gayle Jameson
Collaborators:
Translational Genomics Research Institute
Translational Drug Development
Virgina G. Piper Cancer Center - Clinical Trials
Information provided by (Responsible Party):
Gayle Jameson, Pancreatic Cancer Research Team
ClinicalTrials.gov Identifier:
NCT01893801
First received: July 2, 2013
Last updated: February 27, 2014
Last verified: February 2014
History of Changes
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• No Study Results Posted
• Disclaimer
• How to Read a Study Record
Purpose
The primary objective of this study is to determine the efficacy of nab-paclitaxel plus cisplatin
plus gemcitabine for patients with metastatic pancreatic ductal adenocarcinoma (PDA).

Condition
Stage IV Pancreatic Cancer

Intervention
Drug: nab-paclitaxel
Drug: Cisplatin
Drug: gemcitabine

Study Type:

Interventional

Study Design:

Intervention Model: Single Group Assignment

Phase
Phase 1
Phase 2


Masking: Open Label
Primary Purpose: Treatment
Official Title:

A Phase 1b/2 Pilot Trial of Nab-Paclitaxel Plus Cisplatin Plus Gemcitabine
(Nabplagem) in Patients With Previously Untreated Metastatic Pancreatic
Ductal Adenocarcinoma (PDA)

Resource links provided by NLM:

Drug Information available for: Cisplatin Paclitaxel Gemcitabine Gemcitabine hydrochloride
U.S. FDA Resources
Further study details as provided by Pancreatic Cancer Research Team:
Primary Outcome Measures:
• Complete Response Rate [ Time Frame: 1 yr. ]
The primary objectives of this study is to pursue treatment of 25 individual patients
with previously untreated metastatic pancreatic ductal adenocarcinoma (PDA) to
evaluate:
Complete response rate as defined by computed tomography (CT) scan using RECIST
1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to
normal limits (from at least > 2x ULN). We expect to accomplish this in > or = to 5% of
patients. When a complete response (CR) is documented, a confirmatory PET scan
will be obtained.
If 1 or more of 10 patients demonstrate a complete response (CR), study will continue
to enroll to a total of 25 patients.
If intolerable adverse events or no clinical benefit are noted in the first 6 patients, study
will discontinue enrollment.
Secondary Outcome Measures:
• Evaluate disease control rate [ Time Frame: 9 weeks ]
Evaluate disease control rate (CR, PR and SD at 9 weeks) in patients with metastatic
PDA.
•

Evaluate treatment-related toxicities [ Time Frame: Over the course of the study ]
Evaluate the treatment-related toxicities in this patient population.

•

Evaluate the change in CA 19-9 or other biomarkers [ Time Frame: Over the course of
the study ]

Evaluate the change in CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) in
this patient population.


Estimated Enrollment:

25

Study Start Date:

May 2013

Estimated Study Completion Date:

August 2014

Estimated Primary Completion Date:

May 2014 (Final data collection date for primary
outcome measure)

Arms

Assigned Interventions

Experimental: nab-paclitaxel+Cisplatin+gemcitabine
This is a phase Ib/II open-label, pilot study evaluating the
preliminary efficacy and safety of nab-paclitaxel 125mb/m2,
cisplatin 25mg/m2, and gemcitabine 1000mg/m2, all
administered intravenously (IV) on Days 1 and 8 every 21

days until development of toxicity that is unacceptable in the
opinion of the patient or the Investigator or upon disease
progression.

Drug: nab-paclitaxel
25 mg/m2 given intravenously
(IV) on days 1 and 8 of a 21 day
cycle
Other Name: Abraxane
Drug: Cisplatin
25mg/m2 (or 50mg/m2) given
intravenously (IV) on days 1 and
8 of a 21 day cycle
Other Names:
• cisplatinum
• cisdiamminedichloroplatinum
• CDDP
Drug: gemcitabine
1000mg/m2 given intravenously
(IV) on days 1 and 8 of a 21 day
cycle
Other Name: Gemzar

Detailed Description:
This is a phase 1b/2 open-label pilot study evaluating the preliminary efficacy and safety of
nab-paclitaxel, cisplatin, and gemcitabine in patients with metastatic pancreatic ductal
adenocarcinoma.
An individual cycle of therapy will be defined as Days 1 and 8 every 21 days. Multiple cycles
may be administered until the patient is withdrawn from therapy.
Overall response rates as well as individual categories of response (complete response-CR,

partial response-PR, stable disease-SD and progressive disease-PD) will be determined
using RECIST 1.1. Time-to-event endpoints, including progression free survival (PFS) and
OS (overall survival) will be assessed using the Kaplan-Meier method. Evaluation of stable
disease at 9 weeks will also be assessed. Toxicity (adverse events) will be recorded using the
NCI CTCAE (v4.0, May 2009).
Eligibility


Ages Eligible for Study:
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Criteria

18 Years and older (Adult, Senior)
All
No

Inclusion Criteria:
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Age >18 years of age; male or female.
Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
Capable of providing informed consent and complying with trial procedures.
Karnofsky Performance Status (KPS) of >/=70%.

Life expectancy >/=12 weeks.
Measurable tumor lesions according to RECIST 1.1 criteria.
Women must not be able to become pregnant (e.g. post-menopausal for at least 1
year, surgically sterile, or practicing adequate birth control methods) for the duration of
the study. Women of child bearing potential must have a negative serum or urine
pregnancy test at the Screening Visit and be non-lactating. Both male and female
patients of reproductive potential must agree to use a reliable method of birth control
during the study.

Exclusion Criteria:
•

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Patients must have received no previous radiotherapy, surgery, chemotherapy or
investigational therapy for the treatment of metastatic disease. Prior treatments in the
adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a
radiation sensitizer are allowed, provided at least 6 months have elapsed since
completion of the last dose and no lingering toxicities are present.
Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of
study treatment.

Exposure to any investigational agent within 4 weeks prior to initiation of study
treatment.
Evidence of central nervous system (CNS) metastasis (negative imaging study, if
clinically indicated, within 4 weeks of Screening Visit).
History of other malignancies (except cured basal cell carcinoma, superficial bladder
cancer or carcinoma in situ of the cervix) unless documented free of cancer for >/= 5
years.
Laboratory values: Screening serum creatinine > upper limits of normal (ULN); total
bilirubin > ULN: alanine aminotransferase (ALT) and AST >/= 2.5 ULN or >/= 5.0 x
ULN if liver metastases are present; absolute neutrophil count < 1,500/mm3, platelet
concentration < 100,00/mm3, hematocrit level < 27% for females or < 30% for males,
or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT],
International Normalized Ratio [INR]) > 1.5 x ULN unless on therapeutic doses of
warfarin.
Current, serious, clinically significant cardiac arrhythmias as determined by the
Investigator.
History of HIV infection.
Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or anti-fungals.


•

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Major surgery within 4 weeks prior to initiation of study treatment. Any condition that
might interfere with the patient's participation in the study or in the evaluation of the
study results.
Any condition that is unstable and could jeopardize the patient's participation in the
study.

Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and
family members or friends about deciding to join a study. To learn more about this study, you
or your doctor may contact the study research staff using the Contacts provided below. For
general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01893801
Contacts
Contact: Amy Stoll-D'Astice, MS, CCRP

(602) 358-8319



Locations
United States, Arizona
Scottsdale Health Care
Scottsdale, Arizona, United States, 85260
Contact: Joyce Schaffer, MSN RN AOCNS 480-323-1339
Principal Investigator: Gayle S Jameson, MSN ACNP-BC
Sub-Investigator: Ramesh K Ramanathan, MD
Sub-Investigator: Daniel D Von Hoff, MD FACP
Sub-Investigator: Katy B Schroeder, RN BSN OCN

Recruiting


United States, New Jersey
Rutgers - Cancer Institute of New Jersey (CINJ)
Recruiting
New Brunswick, New Jersey, United States, 08901

Contact: Anjali Krishnan, RN 732-235-8996
Contact: Tatianna Zelinskaya 732-235-9837
Principal Investigator: Elizabeth Popllin, MD
United States, Pennsylvania
Vita Medical Associates, PC
Recruiting
Bethlehem, Pennsylvania, United States, 18015
Contact: Colleen Saitta, NP 610-866-0113
Contact: Gulyun Zhou, NP 610-866-0113
Principal Investigator: Anna A Niewiarowska, MD
Sponsors and Collaborators
Gayle Jameson
Translational Genomics Research Institute
Translational Drug Development
Virgina G. Piper Cancer Center - Clinical Trials


Investigators
Principal Investigator:
More Information

Gayle S Jameson, MSN ACNP-BC

Scottsdale Health Care

Additional Information:
Additional information about the Pancreatic Cancer Research Team (PCRT)
Non-profit Organization
Related link
Non-profit organization for pancreatic cancer research

Publications:
Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai
N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo
M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic
cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi:
10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.
2013 Gastrointestinal Cancers Symposium. Abstract LBA148. Presented January 25, 2013

Responsible Party:

Gayle Jameson, Lead Principal Investigator, Pancreatic Cancer
Research Team

ClinicalTrials.gov Identifier:

NCT01893801

Other Study ID Numbers:

PCRT 12-001

Study First Received:

July 2, 2013

Last Updated:

February 27, 2014

History of Changes

Keywords provided by Pancreatic Cancer Research Team:
pancreatic cancer
pancreatic adenocarcinoma
Stage IV pancreatic cancer
pancreas
pancreatic
Additional relevant MeSH terms:
Pancreatic Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases

Cisplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological
Action
Antimetabolites, Antineoplastic


Carcinoma

Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel

Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 25, 2017