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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00429858
Recruitment Status : Terminated (Study accrual rate is very slow, it was mandated by NCI to be terminated.)
First Posted : February 1, 2007
Results First Posted : September 18, 2020
Last Update Posted : September 18, 2020
Sponsor:
Collaborators:
Eli Lilly and Company
Taiho Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Andrew Ko, University of California, San Francisco

Brief Summary:

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 or disease Intervention/treatment Phase
Pancreatic Cancer Drug: S-1 Drug: gemcitabine hydrochloride Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Individualized Management of Pancreatic Cancer With Targeted Therapeutics (IMPACTT): A Phase II Clinical Trial
Actual Study Start Date : January 22, 2007
Actual Primary Completion Date : January 20, 2010
Actual Study Completion Date : January 20, 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Targeted therapy group
Gemcitabine monotherapy until disease progression, followed by gemcitabine + S-1
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)
Other Names:
  • tegafur-gimeracil-oteracil potassium
  • TS-1
  • TS-ONE

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




Primary Outcome Measures :
  1. Correlate Intratumoral Expression Level of Ribonucleotide Reductase Subunit 1 (RRM1) With Response to Gemcitabine in Patients With Advanced Pancreatic Cancer. [ Time Frame: Up to 2 years ]
    Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between RRM1 and response to gemcitabine. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of RRM1 and response to gemcitabine, a value of 0 indicating no association between RRM1 and response to gemcitabine, and a value of +1 indicating a positive linear association of RRM1 and response to gemcitabine.


Secondary Outcome Measures :
  1. 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: Up to 2 years ]
    Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between deoxycytidine kinase (dCK), equilibrative nucleoside transporter 1 (ENT1) and concentrative nucleoside transporters 1 and 3 (CNT1 and CNT3), with response to gemcitabine in a table format. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of intratumoral expression levels and response to gemcitabine, a value of 0 indicating no association between intratumoral expression levels and response to gemcitabine, and a value of +1 indicating a positive linear association of intratumoral expression levels and response to gemcitabine.

  2. 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: Up to 2 years ]
    Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between 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 in a table format. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of intratumoral expression levels and the combination of gemcitabine/S-1, a value of 0 indicating no association between intratumoral expression levels and response to the combination of gemcitabine/S-1, and a value of +1 indicating a positive linear association of intratumoral expression levels and response to the combination of gemcitabine/S-1.

  3. Median Overall Survival [ Time Frame: Up to 2 years ]
    Overall survival will be defined from the date of receiving the first treatment until death

  4. Number of Patients With Dose Modifications [ Time Frame: 8 weeks after 6th patient is enrolled ]
    Treatment-related toxicities resulting in a dose modification be classified using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3 will be tabulated.

  5. Percentage of Patients Classified as Potential Biomarker Responders [ Time Frame: Assessed after the first 5 weeks of treatment ]
    Defined as the percentage of patients who will be categorized as potential biomarker responders if their CA19-9 has declined by > 10 % from peak value (peak value may have been at either week 1 or 3) during the initial gemcitabine monotherapy phase

  6. Median Time to Progression [ Time Frame: Up to 2 years ]
    Time to progression will be summarized according to the method of Kaplan and Meier

  7. Percentage of Patients With at Biomarker Response [ Time Frame: Up to 2 years ]
    A biomarker response for any given line of therapy is defined as patients with a baseline CA19-9 level > 75 units per cubic centimeter (U/cc) who demonstrate a > 25% decline in their peak CA19-9 level, sustainable for at least 2 consecutive measurements



Information from the National Library of Medicine

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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

  • 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).

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): NCT00429858


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Andrew Ko
Eli Lilly and Company
Taiho Pharmaceutical Co., Ltd.
Investigators
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Study Chair: Andrew Ko, MD University of California, San Francisco
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Responsible Party: Andrew Ko, Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00429858    
Other Study ID Numbers: 06456
NCI-2011-01215 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
UCSF-H12191-29556-01 ( Other Identifier: UCSF California CHR Approval # )
First Posted: February 1, 2007    Key Record Dates
Results First Posted: September 18, 2020
Last Update Posted: September 18, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andrew Ko, University of California, San Francisco:
recurrent pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Gemcitabine
Tegafur
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs