Back to resultsA Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
Primary Purpose
Pancreatic Cancer, Biliary Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
5-FU
Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Gemcitabine, Infusional 5-Fluorouracil,Cisplatin, Advanced Pancreatic and Biliary Cancers, untreated & previously treated pancreatic & biliary cancer.
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- University of Michigan Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Gemcitabine, 5-FU and Cisplatin
Arm Description
4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Median Overall Survival of Previously Treated and Previously Untreated Patients
To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.
Full Information
NCT ID
NCT01661114
First Posted
July 24, 2012
Last Updated
September 1, 2016
Sponsor
University of Michigan Rogel Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT01661114
Brief Title
A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
Official Title
A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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:
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.
Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression, mucositis and diarrhea.
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Biliary Cancer
Keywords
Gemcitabine, Infusional 5-Fluorouracil,Cisplatin, Advanced Pancreatic and Biliary Cancers, untreated & previously treated pancreatic & biliary cancer.
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gemcitabine, 5-FU and Cisplatin
Arm Type
Experimental
Arm Description
4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
5-Fluorouracil
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Primary Outcome Measure Information:
Title
The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Median Overall Survival of Previously Treated and Previously Untreated Patients
Description
To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Zalupski, MD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Citations:
Citation
Colucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et al., 2009, Heinemann et al., 2008, Valle et al., 2010
Results Reference
background
Learn more about this trial
A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
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