Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer

This study has been terminated.
(Study accrual rate is very slow, it was mandated by NCI to be terminated.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00429858
First received: January 30, 2007
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors predict a patient's response to treatment and help plan the best treatment.

PURPOSE: This phase II trial is studying gene expression in predicting treatment response in patients receiving gemcitabine and S-1 for locally advanced unresectable or metastatic pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Drug: S-1
Drug: gemcitabine hydrochloride
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Individualized Management of Pancreatic Cancer With Targeted Therapeutics (IMPACTT): A Phase II Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • • To correlate intratumoral expression level of ribonucleotide reductase subunit 1 (RRM1) with response to gemcitabine in patients with advanced pancreatic cancer. [ Time Frame: 2 years after the last patient is enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To correlate intratumoral expression levels of other genes, including deoxycytidine kinase (dCK), equilibrative nucleoside transporter 1 (ENT1) and concentrative nucleoside transporters 1 and 3 (CNT1 and CNT3), with response to gemcitabine. [ Time Frame: 2 years after the last patient is enrolled ] [ Designated as safety issue: No ]
  • • To correlate intratumoral expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (ORPT) with response to the combination of gemcitabine/S-1. [ Time Frame: 2 years after the last patient is enrolled ] [ Designated as safety issue: No ]
  • • To estimate median survival using the therapeutic strategy outlined herein, entailing sequential addition of agents and decision-making based on early CA19-9 biomarker response. [ Time Frame: 2 years after the last patient is enrolled ] [ Designated as safety issue: No ]
  • To determine the safety of this approach. [ Time Frame: 8 weeks after 6th patient is enrolled ] [ Designated as safety issue: Yes ]
  • • To determine the percentage of patients classified as potential biomarker responders (during the initial gemcitabine monotherapy phase). [ Time Frame: 2 years afetr the last patient is enrolled ] [ Designated as safety issue: No ]
  • • To calculate the time to progression on each successive line of treatment. [ Time Frame: 2 years after the last patient is enrolled ] [ Designated as safety issue: No ]
  • • To calculate the proportion of patients with at least 25% decline in CA 19-9 biomarker (= "biomarker response") on each successive line of treatment. [ Time Frame: 2 years after the last patient is enrolled ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: January 2007
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: S-1
    S-1 is given as follows: 25 mg/m2 bid on days 1-7 and 15-21 of the cycle (28 days)
    Drug: gemcitabine hydrochloride
    Patients will receive gemcitabine at a dose of 1,000 mg/m2 i.v. at a fixed-dose rate (FDR) infusion of 10 mg/m2/minute (100 minutes), once a week for 3 consecutive weeks, followed by one week rest. Each 4 week period is referred to as a treatment cycle
    Other Name: Gemzar
  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • Correlate intratumoral expression level of ribonucleotide reductase subunit 1 (RRM1) with response to gemcitabine hydrochloride therapy in patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas.

Secondary

  • Correlate intratumoral expression levels of other genes (e.g., deoxycytidine kinase [dCK], equilibrative nucleoside transporter 1 [ENT1], and concentrative nucleoside transporters 1 and 3 [CNT1 and CNT3]) with response in these patients.
  • Determine, preliminarily, the median survival of these patients, using a therapeutic strategy entailing sequential addition of agents and decision making based on early CA 19-9 biomarker response.
  • Determine the safety of this approach.
  • Determine the percentage of patients classified as potential biomarker responders.
  • Determine the time to progression with each successive line of treatment.
  • Determine the proportion of patients with ≥ 25% decline in CA 19-9 biomarker (i.e., biomarker response) with each successive line of treatment.

Tertiary

  • Identify other genes that may mediate sensitivity to gemcitabine hydrochloride, S-1, and other agents with activity in pancreatic cancer.
  • Determine the frequency of host genetic polymorphisms in various nucleoside transporters.

OUTLINE: This is a multicenter.

  • Initial treatment (gemcitabine hydrochloride alone): Patients receive gemcitabine hydrochloride IV over 100 minutes on days 1, 8, and 15. CA 19-9 levels are assessed in weeks 1 and 3 of each course. Patients who are biomarker responders continue to receive treatment with gemcitabine hydrochloride alone. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who are no longer biomarker responders or show other evidence of disease progression proceed to therapy comprised of gemcitabine hydrochloride and S1.
  • Gemcitabine hydrochloride and S-1 treatment: Patients receive gemcitabine hydrochloride IV over 100 minutes on days 1 and 15 and oral S-1 twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo core needle tumor biopsy and fine-needle aspiration at baseline. Tissue samples are analyzed for correlation between transcript and protein expression by immunohistochemistry and for expression of genes and gene products that may mediate sensitivity to gemcitabine hydrochloride (RRM1, ENT1, CNT1 and 3, dCK); S-1, thymidine phosphorylase [TP], TS, DPD, and ORPT; and other anticancer treatments (ERCC-1, epidermal growth factor receptor, GSK-3β) by reverse-transcriptase polymerase chain reaction. Tissue samples are also analyzed by microarray and comparative genomic hybridization to identify new genes that may predict chemotherapeutic response or mediate sensitivity to anticancer therapy. Mutational status of KRAS and p53 gene are also assessed.

Blood samples are collected at baseline and are analyzed by genotyping assays to identify polymorphic variants of select genes.

After completion of study treatment, patients are followed monthly.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Adenocarcinoma of the pancreas that is already or will be histologically or cytologically proven.
  • Patients must have either locally advanced (unresectable) or metastatic disease.
  • Radiographically measurable disease is not required.
  • No prior therapy for advanced pancreatic cancer. Treatment given in the adjuvant setting (radiation and/or chemotherapy, given either concurrently or systemically) does not count as prior therapy as long as progressive disease occurs > 6 months following completion of treatment.
  • Greater than or equal to 18 years of age.
  • ECOG performance status of 0 or 1 (See Appendix D).
  • Laboratory criteria:
  • ANC > 1500/µL
  • Platelet count > 100,000/µL
  • Hemoglobin > 9 g/dL (may be transfused or receive epoetin alfa to maintain or exceed this level)
  • INR < 1.5 (except those subjects who are receiving full-dose warfarin
  • Total bilirubin < 2.0 mg/dL
  • AST or ALT < 5 times upper limit of normal for subjects with documented liver metastases; < 2.5 times the upper limit of normal for subjects without evidence of liver metastases
  • Serum creatinine < 2.0 mg/dL
  • Serum CA19-9 > 2X upper limits of normal.
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
  • Women or men of reproductive potential must agree to use an effective contraceptive method during treatment and for 6 months afterwards.

Exclusion criteria

  • Inability to comply with study and/or follow-up procedures
  • Disease determined to be not amenable to biopsy upon review of radiographs by the oncologist and/or interventional radiologist.
  • Clearly resectable disease in a patient who is an appropriate operative candidate.
  • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
  • Prior systemic therapy for advanced pancreatic cancer
  • Pregnant (positive pregnancy test) or lactating
  • Use of anti-neoplastic or anti-tumor agents not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study.
  • Use of concurrent investigational agents is not permitted.

S-1 Specific Exclusion Criteria

  • Is receiving a concomitant treatment with drugs interacting with S-1. The following drugs are prohibited because there may be an interaction with S-1:
  • Sorivudine, brivudine, uracil, dipyridamole, cimetidine, and folinic acid (may enhance S-1 activity).
  • Allopurinol (may diminish S-1 activity).
  • Phenytoin (S-1 may enhance phenytoin activity).
  • Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and flucytosine activity).
  • Pilocarpine (may inhibit cytochrome P-450 enzyme 2A6 activity).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429858

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
University of California, San Francisco
Investigators
Study Chair: Andrew Ko, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00429858     History of Changes
Other Study ID Numbers: CDR0000525724, P30CA082103, UCSF-06456, UCSF-H12191-29556-01
Study First Received: January 30, 2007
Last Updated: October 14, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
recurrent pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014