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

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ClinicalTrials.gov Identifier: NCT01661114
Recruitment Status : Completed
First Posted : August 9, 2012
Results First Posted : February 4, 2016
Last Update Posted : October 19, 2016
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Biliary Cancer Drug: Gemcitabine Drug: 5-FU Drug: Cisplatin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
Study Start Date : July 2011
Actual Primary Completion Date : December 2014
Actual Study Completion Date : March 2016


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
Other Name: 5-Fluorouracil

Drug: Cisplatin



Primary Outcome Measures :
  1. The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment [ Time Frame: 28 days ]

    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 :
  1. Median Overall Survival of Previously Treated and Previously Untreated Patients [ Time Frame: 1 year ]
    To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01661114


Locations
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United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Mark Zalupski, MD University of Michigan Rogel Cancer Center

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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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT01661114     History of Changes
Other Study ID Numbers: UMCC 2011.036
HUM 49518 ( Other Identifier: University of Michigan IRBMED )
First Posted: August 9, 2012    Key Record Dates
Results First Posted: February 4, 2016
Last Update Posted: October 19, 2016
Last Verified: September 2016

Keywords provided by University of Michigan Rogel Cancer Center:
Gemcitabine, Infusional 5-Fluorouracil,Cisplatin
Advanced Pancreatic and Biliary Cancers
untreated & previously treated pancreatic & biliary cancer.

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Biliary Tract Diseases
Cisplatin
Gemcitabine
Fluorouracil
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs