Clinical trial NCT01661114: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Biliary Cancer
Keywords: Gemcitabine, Infusional 5-Fluorouracil,Cisplatin
Advanced Pancreatic and Biliary Cancers
untreated & previously treated pancreatic & biliary cancer.
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2012-08-09
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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:

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.

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.

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.

Primary outcomes:
measure: The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment
timeFrame: 28 days
Secondary outcomes:
measure: Median Overall Survival of Previously Treated and Previously Untreated Patients
timeFrame: 1 year
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Mark Zalupski, MD
role: PRINCIPAL_INVESTIGATOR
References:
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