A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Cancer, Cancer, Pancreatic Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | July 2011 |
| End Date: | July 2016 |
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.
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.
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.
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.
We found this trial at
1
site
1500 East Medical Center Drive
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
800-865-1125
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
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