Phase III Study of S-1 + Cisplatin vs Cisplatin in Cervical Cancer

Study Overview
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Brief Summary
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This study is an open-label, multicenter, multinational, two-arm, parallel randomized Phase 3 study evaluating the efficacy and safety of S-1+Cisplatin versus single-agent Cisplatin in patients with stage IVB, recurrent or persistent carcinoma of the cervix.

Detailed Description
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Japanese phase II study of S-1 in cervical cancer suggested promising response rate and good tolerability. Since recommended chemotherapy for metastatic or recurrent cervical carcinoma is either single-agent Cisplatin or Cisplatin-based combination chemotherapy, this is designed to evaluate the efficacy and safety of S-1 in combination with Cisplatin compared with single-agent Cisplatin.

Official Title
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Phase III Study of S-1 + Cisplatin Compared With Single-agent Cisplatin in Stage IVB, Recurrent, or Persistent Carcinoma of the Cervix

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: S-1 + Cisplatin (arm A)
* Drug: Cisplatin (arm B)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven cervical carcinoma (All histological subtype will be included). Patients who have stage IVB, recurrent or persistent disease. Patients who are not amenable to curative treatment with surgery and/or radiotherapy. Patients who have not received chemotherapy or chemoradiotherapy after diagnosis of recurrent, persistent, or stage IVB disease. If the patient have received chemotherapy, radiotherapy or chemoradiotherapy as previous treatment, following interval must have elapsed from the last administration of treatment: Chemotherapy: 21 days Radiotherapy: 21 days* Chemoradiotherapy: 42 days* If there have been residual disease in previously irradiated field and without disease progression since the (chemo) radiotherapy, 90 days must have elapsed after the last administration of irradiation. Patients who have adequate hematologic, hepatic and renal functions as defined below: Hemoglobin: ≥ 8.0 g/dL Neutrophil count: ≥ 2,000/mm^3 Platelet count: ≥ 100,000/mm^3 Total serum bilirubin: ≤ 1.5 times the upper limits of normal (ULN) AST (GOT), ALT (GPT): ≤ 2.5 times the ULN. If abnormal values are associated with hepatic metastasis: ≤ 5.0 times the ULN Serum creatinine: ≤ ULN or creatinine clearance: ≥ 50 ml/min Patients who have an ECOG performance status : 0-1. Age: ≥ 20 years old. Patients who can take pills orally. Patients who signed the written consent form. Exclusion Criteria: Patients who have known hypersensitivity to 5-FU or Cisplatin. Patients who are receiving concomitant treatment with drugs interacting with S-1. Patients who are receiving concomitant treatment with drugs interacting with Cisplatin. Patients who were administered other investigational products within 30 days before the initiation of study treatment. Patients who were previously treated with S-1. Patients who had received platinum-containing chemotherapy or chemoradiotherapy and whose disease progressed during the therapy. Patients who suffer from active infection (e.g. fever ≥ 38°C). Patients who have serious complications. Patients with bleeding which requires hemostasis treatment. Patients with bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. Patients with uncontrolled pleural effusion and/or ascites requiring drainage at least twice a week. Patients with symptomatic brain metastasis or history of brain metastasis. Patients who have unmanageable bowel movement (ex. Watery stool, chronic constipation). Patients with active double cancer. Patients who are pregnant or lactating. Patients who are considered to be inappropriate to the subject of this study by the investigator.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>S-1 + Cisplatin (arm A) | Drug: S-1 + Cisplatin (arm A)<br>* S-1 will be administered orally, twice daily from Day 1 through Day 14 followed by a recovery period from Days 15 through Day 21. Initial dose of S-1 will be determined according to the patient's body surface area (80 to 120 mg/day). On Day 1, Cisplatin 50 mg/m2 will be administered intravenously (IV). This regimen is to be repeated every 3 weeks.<br>|
| Active Comparator: 2<br>Cisplatin (arm B) | Drug: Cisplatin (arm B)<br>* Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From the date of randomization to death from any cause, assessed up to 296 events or the end of November 2015, whichever was earlier, each three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival, Safety | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | About Progression free survival, from the randomization to disease progression or death, whichever came first, assessed up to until primary outcome came each three months, and about safety, from the first treatment to 30 days after the last treatment |