A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
18 Years
N/A
Both
Pancreatic Cancer, Biliary Cancer
Trial Information
A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
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 synergisim that has been observed with platinum/5FU and platinum/gemcitabine
combinations(Colucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et
al., 2009, Heinemann et al., 2008, Valle et al., 2010).
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 performance status < 1
- 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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate
Outcome Description:
The primary objective of this clinical trial is to estimate the best objective 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.
Outcome Time Frame:
28 days
Safety Issue:
No
Principal Investigator
Mark Zalupski, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Michigan Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
UMCC 2011.036
NCT ID:
NCT01661114
Start Date:
July 2011
Completion Date:
July 2016
Related Keywords:
- Pancreatic Cancer
- Biliary Cancer
- Gemcitabine, Infusional 5-Fluorouracil,Cisplatin
- Advanced Pancreatic and Biliary Cancers
- untreated & previously treated pancreatic & biliary cancer.
- Pancreatic Neoplasms
- Biliary Tract Neoplasms
Name | Location |
|---|---|
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
