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

NCT00429858 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 06456NCI-2011-01215UCSF-H12191-29556-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Pancreatic Cancer

Keywords

recurrent pancreatic cancer; stage III pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Correlate Intratumoral Expression Level of Ribonucleotide Reductase Subunit 1 (RRM1) With Response to Gemcitabine in Patients With Advanced Pancreatic Cancer.

  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.

  Up to 2 years

Secondary Outcomes (7)

• 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.

  Up to 2 years

• 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.

  Up to 2 years

• Median Overall Survival

  Up to 2 years

• Number of Patients With Dose Modifications

  8 weeks after 6th patient is enrolled

• Percentage of Patients Classified as Potential Biomarker Responders

  Assessed after the first 5 weeks of treatment

Study Arms (1)

Targeted therapy group

EXPERIMENTAL

Gemcitabine monotherapy until disease progression, followed by gemcitabine + S-1

Drug: S-1; Drug: gemcitabine hydrochloride

Interventions

S-1 DRUG

S-1 is given as follows: 25 mg/m2 bid on days 1-7 and 15-21 of the cycle (28 days)

Also known as: tegafur-gimeracil-oteracil potassium, TS-1, TS-ONE

Targeted therapy group

gemcitabine hydrochloride DRUG

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

Also known as: Gemzar

Targeted therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Andrew Ko: lead
• Eli Lilly and Company: collaborator
• Taiho Pharmaceutical Co., Ltd.: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

S 1 (combination); titanium silicide; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Historical records were discarded in accordance with university record retention policy. Data electronically archived to the current clinical trial management system has been reported where possible.

Results Point of Contact

• Title: Dr. Andrew Ko, MD
• Organization: University of California, San Francisco

Andrew.Ko@ucsf.edu

(415) 353-7286

Study Officials

• Andrew Ko, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2007
• First Posted: February 1, 2007
• Study Start: January 22, 2007
• Primary Completion: January 20, 2010
• Study Completion: January 20, 2010
• Last Updated: September 18, 2020
• Results First Posted: September 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)