GEM vs GEM+TS-1 for Advanced Pancreatic Cancer

Randomized Phase II Study of Gemcitabine (GEM) Versus GEM+TS-1 for Advanced Pancreatic Cancer

The primary objective of this study is to compare tumor response rate of the test arm(gemcitabine+S-1) with the control arm(gemcitabine alone) in patients with unresectable pancreatic cancer

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: gemcitabine + S-1; Drug: gemcitabine

Detailed Description

Pancreatic cancer is the fifth leading cause of cancer death in the United States. It is difficult to diagnose at its early stage and only 10-20% of patients are candidates for resection with 5-year survival rate of less than 10%. Patients with unresectable pancreatic cancer has a poor prognosis. Gemcitabine, a cytidine analogue, is the standard chemotherapeutic agent for the disease with median survival time(MST) ranging from 6 to 8 months. Phase Ⅲ study showed that combinations with other drugs, such as oxaliplatine or CDDP, did not contribute to survival time. TS-1, a new oral fluoropyrimidine which consists of the 5-FU prodrug tegafur (ftorafur, FT) and two enzyme inhibitors, CDHP (5-chloro-2,4-dihydroxypyridine) and OXO (potassium oxonate), in a molar ratio of 1(FT):0.4 (CDHP):1(OXO), is commercially available since late 90'in Japan. Phase II trials have demonstrated that S-1 was effective as a single agent for treatment of gastric (RR 44.6%), colorectal (RR 37.4%), head and neck, breast, non-small cell lung, and pancreatic cancers(20%). A combination of gemcitabine and TS-1 is found to be effective and promising in phase Ⅱ trial for metastatic pancreatic carcinoma in selected subjects, but the combination therapy has high rate of side effects. This phase Ⅱ randomized controlled study compares efficacy and feasibility of GEM+S-1 with GEM alone in patients with locally advanced and metastatic pancreatic cancer and performance status of 0-2, aiming at patients in rather ordinary clinical settings.

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 135-8550
    • Cancer Institute Ariake Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically proven unresectable pancreatic carcinoma
2. There must be measurable lesions with multislice CT
3. ECOG Performance status 0-2
4. No other active cancer
5. No previous therapy such as radiotherapy, chemotherapy and immunotherapy
6. Adequate organ functions are preserved as WBC more than 4000/mm3,Hb more than 8.0g/dl,neutrophil more than 2000/mm3,platlet more than 100,000/mm3, AST less than 2.5 x normal or less than 5.0 x normal if the patient had known liver metastasis, bilirubin less than 2.0mg/dl, Ccr more than 60ml/min
7. No serious complications
8. Be able to eat food
9. Life expectancy of more than 8 weeks duration
10. Informed consent is obtained-

Exclusion Criteria:

1. Interstitial pneumonia
2. Uncontrollable diabetes, liver dysfunction, angina pectoris,or myocardial infarction with its onset within 3 months
3. Serious infection
4. Pregnant or lactating females
5. History of serious drug allergy
6. Serious other complications
7. Uncontrolled mental disorders -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; gemcitabine + S-1	Drug: gemcitabine + S-1; gemcitabine on day one and 8th S-1 po days 1 to14 every 3 weeks; Other Names: gemzar; TS-1
Active Comparator: 2; S-1	Drug: gemcitabine; gemcitabine DIV on day one , 8th and 15th; Other Names: gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
response rate	during observation

Secondary Outcome Measures

Outcome Measure	Time Frame
median survival time(MST)	during observation
time-to-progression(TTP)	from onset of regression to progression
toxicity	during observation
clinical benefit response	during observation

Collaborators and Investigators

• Sponsor: Japan Clinical Cancer Research Organization
• Investigators: Principal Investigator: Takaaki Ikari, MD. PhD, Cancer Institute Ariake Hospital; Principal Investigator: Masafumi Suyama, M.D. PhD, Juntenndo University Hospital; Principal Investigator: Naoto Egawa, M.D. PhD, Komagome Hospital; Principal Investigator: Yasuji Omuro, M.D. PhD, Komagome Hospital; Principal Investigator: Takao Itoi, M.D. PhD, Tokyo medical college; Principal Investigator: Atsushi Sofuni, M.D. PhD, Tokyo medical college

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: August 8, 2007
• First Submitted That Met QC Criteria: August 8, 2007
• First Posted (Estimate): August 9, 2007

Study Record Updates

• Last Update Posted (Estimate): June 28, 2011
• Last Update Submitted That Met QC Criteria: June 27, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: S-1; gemcitabine; pancreatic carcinoma; phaseⅡstudy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: JACCRO PC-01