Phase 2 Study of S-1 as 2nd Line Therapy in Metastatic Pancreatic Cancer

NCT ID: NCT00652054

Last Updated: 2024-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2007-10-31

Brief Summary

The purpose of this study is to determine whether S-1 is effective as 2nd line therapy in slowing tumor activity in patients with metastatic pancreatic cancer who have previously received 1st line treatment with a gemcitabine regimen. The study is also looking at the safety of S-1.

Detailed Description

Metastatic pancreatic cancer is relatively unresponsive to chemotherapy. This is true for the nucleoside analogue gemcitabine, with a response rate of approximately 10%, as well as for 5-fluorouracil (5-FU). Even when gemcitabine is combined with other chemotherapeutic drugs or biological agents, the overall tumor response rate remains basically unchanged. S-1 is a new generation oral fluoropyrimidine that combines Tegafur (5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione [FT]), an oral prodrug of 5-FU, with two modulators, Gimeracil (5-chloro-2,4-dihydroxypyridine [CDHP]), which inhibits 5-FU degradation by dihydropyrimidine dehydrogenase (DPD) inhibition, and Oteracil potassium (Oxo), which inhibits 5-FU phosphorylation in the digestive tract. This combination of 3 compounds is designed to achieve enhanced antitumor activity while decreasing gastrointestinal toxicity.

Conditions

Metastatic Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks.

Group Type: EXPERIMENTAL

S-1

Intervention Type: DRUG

All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. The trial will proceed to the second stage only if sufficient efficacy is demonstrated in Stage 1.

Interventions

S-1

All patients will receive S-1 orally at a dose of 30 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. The trial will proceed to the second stage only if sufficient efficacy is demonstrated in Stage 1.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Has provided written informed consent. 2. Has histologically or cytologically confirmed locally advanced, unresectable or metastatic adenocarcinoma of the pancreas not amenable to curative radiotherapy or surgery.

3. Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ie, lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral computed tomography [CT] scan).

4. Is able to take medications orally. 5. Is 18 years of age or older. 6. Has a Karnofsky Performance Status (KPS) ≥ 70% (see Appendix A). 7. Has a life expectancy of ≥ 12 weeks. 8. Has adequate organ function as defined by the following criteria:

1. Transaminases AST (SGOT) and ALT (SGPT) ≤ 2.5 times the upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastasis, then AST (SGOT) and ALT (SGPT) may be ≤ 5 times ULN.

2. Total serum bilirubin ≤ 3.0 times ULN (if due to underlying liver metastasis, then total bilirubin may be ≤ 5 times ULN).

3. Absolute granulocyte count ≥ 1,500/mm3 (ie, ≥ 1.5 x 109/L by International Units [IU]).

4. Platelet count ≥ 100,000/mm3 (IU: ≥ 100 x 109/L).

5. Hemoglobin value ≥ 9.0 g/dL.

6. Calculated creatinine clearance ≥ 60 mL/min (based on serum creatinine) (Cockcroft-Gault85 formula) 9. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria

• 1. Has had treatment with any of the following within the specified time frame prior to study drug administration:

1. Any prior anticancer chemotherapy.

2. Radiation therapy to a target lesion unless there was evidence of PD after radiotherapy (and this target lesion must not be the only site of measurable disease).

3. Any radiotherapy within the previous 3 weeks.

4. Any investigational agent received either concurrently or within the last 30 days.

5. Current enrollment in another clinical study with an investigational agent. Patients participating in surveys or observational studies are eligible to participate in this study.

2. Major surgery within the previous 3 weeks. 3. Symptomatic brain metastasis not controlled by corticosteroids. 4. Leptomeningeal metastasis. 5. Previous or concurrent malignancy other than pancreatic cancer except adequately treated carcinoma in-situ of the cervix or non-melanoma skin cancer. 6. Uncontrolled ascites requiring drainage at least twice a week. 7. Other serious illness or medical condition(s) including, but not limited to, the following:

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1. Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class III or IV), angina pectoris, arrhythmias, or hypertension.

2. Active infection.

3. Known (at time of entry) gastrointestinal disorder, including malabsorption, chronic nausea, vomiting, or diarrhea, present to the extent that it might interfere with oral intake and absorption of study medication.

4. Poorly controlled diabetes mellitus.

5. Psychiatric disorder that may interfere with consent and/or protocol compliance.

6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.

8. 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:

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1. Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1 activity).

2. Allopurinol (may diminish S-1 activity).

3. Phenytoin (S-1 may enhance phenytoin activity).

4. Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and flucytosine activity).

9. Is a pregnant or lactating female. 10. Has known sensitivity to 5-FU. 11. Is a patient with reproductive potential who refuses to use an adequate means of contraception (including male patients).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Taiho Pharma USA, Inc.

Principal Investigators

Fabio Benedetti, MD

Role: STUDY_DIRECTOR

Taiho Oncology, Inc.

Other Identifiers

TPU-S1201

Identifier Type: -

Identifier Source: org_study_id

NCT00227604

Identifier Type: -

Identifier Source: nct_alias