A Trial Of Gemcitabine, Infusional 5-Fluorouracil And Cisplatin For Advanced Pancreatic And Biliary Cancers

Study Overview

A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers

Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers leading to responses in a substantial minority and increasing survival. The use of the FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical experience within the University of Michigan Pancreatic Program leads to an expectation of tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative to FOLFIRINOX include: 1. Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at least as good as irinotecan (probably better, especially when delivered by FDR [fixed-dose rate] infusion) and gemcitabine is much better tolerated with less diarrhea, nausea/emesis, myelosuppression and alopecia. 2. Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression, mucositis and diarrhea. 3. Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold aggravated dysesthesia. Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the investigators believe this treatment may be more widely applicable to pancreatic-biliary cancer patients, including those with advanced disease as well as being considered for use in locally advanced and neo- and adjuvant settings.

Gemcitabine combined with 5FU may enhance the activity of 5-FU in vivo. Gemcitabine is an inhibitor of ribonucleotide reductase, an enzyme needed for synthesis of deoxynucleotides, and 5-FU interferes with dTTP synthesis by inhibition of thymidylate synthase (TS). It is likely that concomitant administration of gemcitabine and 5FU results in increased cytotoxicity by reducing intracellular dTTP thru two different mechanisms, thereby inhibiting DNA replication and repair. Platinum compounds lead to cell death by forming DNA adducts and causing double strand breaks. By inhibiting DNA synthesis and repair, both gemcitabine and 5-FU potentiate the activity of cisplatin. These interactions underlie the clinical synergism that has been observed with platinum/5FU and platinum/gemcitabine combinations.

Pancreatic Cancer
Biliary Cancer

DRUG: Gemcitabine
DRUG: 5-FU
DRUG: Cisplatin

UMCC 2011.036
HUM 49518 (OTHER Identifier) (OTHER: University of Michigan IRBMED)

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-07-24	Results First Submitted 2016-01-05	Last Update Submitted that met QC Criteria 2016-09-01
First Submitted that Met QC Criteria 2012-08-06	Results First Submitted that Met QC Criteria 2016-01-05	Last Update Posted (ESTIMATED) 2016-10-19
First Posted (ESTIMATED) 2012-08-09	Results First Posted 2016-02-04	Last Verified 2016-09

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Gemcitabine, 5-FU and Cisplatin 4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity	DRUG: Gemcitabine DRUG: 5-FU DRUG: Cisplatin

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Gemcitabine, 5-FU and Cisplatin

4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity

DRUG: Gemcitabine

DRUG: 5-FU

DRUG: Cisplatin

Primary Outcome Measures	Measure Description	Time Frame
The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment	The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients. Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	28 days

Secondary Outcome Measures	Measure Description	Time Frame
Median Overall Survival of Previously Treated and Previously Untreated Patients	To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.	1 year

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must have histologic or cytologic diagnosis of pancreatic adenocarcinoma or biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma or gallbladder carcinoma).
Patients must have clinical/radiologic evidence of metastatic disease.
Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin. Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents.
ECOG (Eastern Cooperative Oncology Group) performance status < 1 (A measure of quality of life where 0 represents asymptomatic and 5 represents death).
Patients must have adequate bone marrow (absolute neutrophil count >1,500/mm3, platelet count >100,000/mm3) and renal function (serum creatinine < 1.25 x ULN).
Patients must have at least one measurable lesion per RECIST criteria.
Patients must be free of serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy.
Previous malignancies are permitted provided that they have been treated with curative intent and patient is without evidence of active systemic disease.
Patients must be informed of the investigational nature of this study and provide written informed consent prior to receiving protocol treatment.

Patients with pre-existing peripheral neuropathy > grade 2 are ineligible.
Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin.
Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents.
Serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy.

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Mark Zalupski, MD, University of Michigan Rogel Cancer Center

Publications

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

General Publications

Colucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et al., 2009, Heinemann et al., 2008, Valle et al., 2010

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Resources

PatientS

Caregivers

Clinical Trial Record