Gemcitabine+Nab-paclitaxel and FOLFIRINOX and Molecular Profiling for Patients With Advanced Pancreatic Cancer

August 17, 2016 updated by: Pancreatic Cancer Research Team

A Phase II Study of Induction Consolidation and Maintenance Approach for Patients With Advanced Pancreatic Cancer

The Investigators in the PCRT team have developed a therapeutic regimen which attacks both the tumor compartment and the stromal compartment of pancreatic cancer and induces complete responses in a small percentage of patients with advanced stage IV pancreatic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators in the PCRT team have developed a therapeutic regimen which attacks both the tumor compartment and the stromal compartment of pancreatic cancer and induces complete responses in a small percentage of patients with advanced stage IV pancreatic cancer.

The gemcitabine + nab-paclitaxel regimen had outstanding activity in a 67 patient phase I/II trial with all patients at the recommended phase II doses (n=44) having a decrease in CA19-9, some complete responses and a median survival of 12.2 months. The proposed regimen that is devised for this study is a bold, innovative approach with the specific aim of utilizing a relentless pursuit approach to try to make the complete response rate >70% and have this response be durable (which the PCRT has defined as lasting at least 6 months) and to dramatically enhance the percent of patients who survive one year (try to make the rate >70%).

The induction regimen the investigators propose collapses the stroma (gemcitabine + nab-paclitaxel) and addresses the use of a non-cross resistant active regimen (FOLFIRINOX) as a consolidation regimen. Both should improve the chance of driving tumor markers down dramatically. The investigators think that FOLFIRINOX with the stromal collapse induced by the initial regimen, plus the totally non-cross resistant shot against the disease (consolidation), will maximize the chance of achieving a complete response with an attendant improvement in survival.

After the consolidation, the patient will be maintained on a less toxic targeted therapy selected by molecular profiling plus the use of the antimetabolomic agent metformin which has consistently been associated with better survival in multiple retrospective studies (Jiralerspong et al., 2009).

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • TGen Clinical Research Services (TCRS)
    • California
      • Burbank, California, United States, 91505
        • Disney Family Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Virginia Piper Cancer Institute (VPCI)
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center
      • Spokane, Washington, United States, 99218
        • Evergreen Hematology and Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically documented Stage IV metastatic adenocarcinoma of the pancreas with measurable disease
  • Performance status ECOG 0 or 1
  • Patients may not have received prior treatment for metastatic pancreatic adenocarcinoma except for receiving gemcitabine or 5FU as a radiosensitizer along with radiation therapy; or have received gemcitabine for adjuvant treatment if they have been off gemcitabine for > 12 months
  • Adult (>18 years of age) male or non-pregnant and non-lactating female
  • A negative serum pregnancy test (Beta-hCG) documented within 72 hours of the first administration of study drug in female patients of child-bearing potential
  • Agreement to use contraception considered adequate and appropriate by the investigator

  • The following blood counts at baseline:

    • ANC >/= 1.5 x 109/L
    • Hgb > 9g/dL
    • Platelets >100 x 109/L

  • The following blood chemistry levels at baseline:

    • AST and ALT </= 2.5 x upper limit of normal range (ULN) or < 5.0 ULN if liver metastasis are present
    • Bilirubin </= ULN
    • Serum creatinine within 1.5 x ULN
  • PT, INR within 1.5 x ULN unless on therapeutic doses of warfarin
  • Must have measurable disease outside the pancreas by RECIST criteria
  • No clinically significant abnormalities in urinalysis results
  • Voluntary agreement to participate in this study after being informed about the nature of the study including potential risks and benefits and having the ability to have questions addressed. The patient must sign and date the IRB approved Informed Consent Form (ICF) prior to participation in any study-related procedures

Exclusion Criteria:

  • Has pancreatic islet cell neoplasms
  • Is pregnant or lactating
  • Has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  • Known infection with HIV, Hepatitis B or Hepatitis C.
  • Patient with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies (see section 4.4.9)
  • Has a serious medical risk factor(s) involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
  • Is unwilling or unable to comply with study procedures.
  • Is enrolled in any other investigational trial.

Caution of observation for interstitial pneumonitis in patients prior to enrollment:

Before enrollment, evaluate candidate patients fro familial, environmental or occupational exposure to opportunistic pathogens, and do not enroll those with a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis. idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gemcitabine & Abraxane Pancreatic Cancer
Gemcitabine+Nab-paclitaxel, FOLFIRINOX, Immunohistochemistry (IHC) Analysis, Metformin and Folfiri
Drug: Gemcitabine
1000 mg/m2 weekly on days 1,8, and 15 in a 28 day cycle. Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).
Other Names:
  • Gemzar
Drug: nab-paclitaxel
125 mg/m2 on days 1,8, and 15 of a 28 day cycle Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).
Other Names:
  • Abraxane
Drug: FOLFIRINOX

The combination below will be given on days 1 and 15 of a 28 day cycle; 5-Fluorouracil 2400 mg/m2 with a 46-hour continuous IV infusion; Leucovorin 400 mg/m2 over a 2 hour IV infusion;

Oxaliplatin 85 mg/m2 as a 2 hour IV infusion; Irinotecan 180 mg/m2 over a 90 minute IV infusion Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).

Other Names:
  • 5-FU
  • Campostar
  • Eloxitan
Genetic: Immunohistochemistry (IHC) Analysis
Immunohistochemistry (IHC) Analysis will be performed on a fresh tissue biopsy of the tumor after chemotherapy has been administered. A targeted-based regimen will be determined from the results of the IHC analysis for the next therapy given to the patient in the maintenance phase of the study.
Drug: Metformin
Metformin 500 mg daily as a 24 hour extended release tablet will also be given as part of the maintenance phase of this study.
Other Names:
  • Glucophage
Drug: mFOLFIRI
5-FU IV infusion, 2400 mg/m2 46h continuous infusion (no bolus 5-FU) treatments per month equaling 1 cycle Leucovorin 400 mg/m2 dl (over a 2 hour IV infusion) Irinotecan 180 mg/m2 dl (over a 90 minute IV infusion) Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate
Time Frame: 1 yr.

The primary objectives of this study are to relentlessly pursue treatment for 34 individual patients with Stage IV pancreatic cancer to obtain:

• The complete response rate (as defined by a complete metabolomic response (CMR) of SUV normalization from baseline, OR a complete response on CT scan using a modified RECIST criteria and CA 19-9 (or CA 125, CEA, or PAM4 if not expressers of CA 19-9) down to normal limits (from at least > 2X ULN).
1 yr.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
One-Year Survival Endpoint
Time Frame: 1 yr.

A secondary objective of this study is to:

Observe the percent of patients who are alive at one year (our goal is to obtain a >70% one year survival.)
1 yr.
Efficacy Endpoints using biomarkers
Time Frame: 1 yr.

A secondary objective of this study is to:

Gather information on other possible efficacy endpoints (e.g. CA 19-9) and other serum/plasma tumor markers
1 yr.
Observing toxicity outcomes
Time Frame: 1 yr.
A secondary objective of this study is to document the toxicities noted in all patients, particularly with those who receive the FOLFIRINOX regimen. Grade 3-4 neutropenia is expected to be > 40% among those receiving FOLFIRINOX, so to minimize toxicity, all patients will receive prophylactic CGSF. In the first 9 patients receiving FOLFIRINOX, if the hospitalization rate due to toxicity is more than 50% (5 or more patients), then all subjects will have a dose reduction to level -1. The incidence of grade 3 and 4 toxicities and dose delays will also be considered for dose modification.
1 yr.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pancreatic Cancer Research Team

Investigators

  • Principal Investigator: Ramesh K Ramanathan, MD, Translational Genomics Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2011

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

November 18, 2011

First Submitted That Met QC Criteria

December 6, 2011

First Posted (Estimate)

December 8, 2011

Study Record Updates

Last Update Posted (Estimate)

August 18, 2016

Last Update Submitted That Met QC Criteria

August 17, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCRT 11-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stage IV Pancreatic Cancer

Clinical Trials on Gemcitabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo, DR of

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe