Phase 1/2 Study of S-1 and Cisplatin in Advanced Gastric Cancer

Taiho Pharma

Status and phase

Completed

Phase 2

Phase 1

Conditions

Gastric Cancer

Treatments

Drug: cisplatin

Drug: S-1

Study type

Interventional

Funder types

Industry

Identifiers

NCT00072787

TPU-S1101 ID02-694;

Details and patient eligibility

About

The purpose of the phase 1 portion of the study is to determine the safe dose of S-1 and cisplatin that can be administered in gastric cancer patients.

The purpose of the phase 2 portion of the study is to determine the antitumor activity of the S-1 and cisplatin regimen established from phase 1 in patients with advanced gastric cancer.

Full description

S-1 is an oral fluoropyrimidine which combines tegafur (a 5-FU prodrug) with two classes of modulators which:

inhibit dihydropyrimidine dehydrogenase (DPD) and
block phosphorylation of 5-FU in gastrointestinal tissues.

S-1 is designed to enhance the the clinical utility of an oral fluoropyrimidine while ameliorating the disadvantage of gastrointestinal toxicity.

5-Fu and cisplatin have been used as a standard treatment in gastric cancer and preliminary data indicate that S-1 plus cisplatin may result in superior tolerability and efficacy in advanced gastric cancer.

S-1 is currently approved in Japan for treatment of gastric cancer and head and neck cancer.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Has histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction
Has advanced, unresectable cancer at the time of study entry
Has measurable disease as defined by RECIST criteria, i.e., 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 CT scan
Is at least 3 weeks post-gastrectomy surgery
Has not received prior chemotherapy for their cancer (adjuvant therapy is permitted and does not count as prior chemotherapy).
Has performance status of ≥ 70% on the Karnofsky scale (Appendix B)
Has a predicted life expectancy of ≥ 12 weeks
Has an absolute granulocyte count of ≥ 1,500/mm3
Has a platelet count ≥ 100,000/mm3
Has a hemoglobin of ≥ 9.0 g/dL
Has a bilirubin of ≤ 1.5 times the ULN
Has transaminases ≤ 2.5 times the ULN except for patients with liver metastasis who may have transaminases ≤ 5 times the ULN
Has a creatinine ≤ ULN and calculated creatinine ≥ 60 mL/min
According to the judgment of the Investigator, the patient has recovered from all previous anti-cancer treatment-related toxicities to at least Grade 1 (see exceptions above)
Has stopped all previous investigational drugs at least 4 weeks prior to treatment with S-1 and cisplatin.
Is able to take medications orally
Female patients of childbearing potential who are not pregnant and who use acceptable means of contraception while on study and for an additional 30 days after the last dose of study medication. Male patients must use adequate contraception.

Exclusion Criteria

Has relapsed within 6 months from the end of adjuvant therapy
Has known brain or leptomeningeal metastases.
Has any other serious illness or medical condition(s) including, but not limited to, the following:
- uncontrolled congestive heart failure, angina pectoris, arrhythmias, or hypertension ; or any significant medical condition that is a contraindication for chemotherapy
- concurrent malignancy other than gastric cancer except adequately treated carcinoma-in-situ of the cervix or non-melanoma skin cancer
- active infection
- gastrointestinal disorder, including malabsorption, chronic nausea and vomiting, chronic diarrhea
- unstable diabetes mellitus
- psychiatric disorder that may interfere with consent and/or protocol compliance
- known neuropathy (including hearing loss) at baseline of Grade 2 or higher (as per NCI CTC v2.0 see Appendix A)
Has known hypersensitivity to any of the constituents of the study medication
Is receiving a concomitant treatment with drugs interacting with S-1.
Is a pregnant or lactating female or who refuses to use an acceptable means of contraception. Is a male and refuses to use an acceptable means of contraception.