Cervical Cancer
Conditions
Brief summary
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
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.
Interventions
DRUGS-1 + Cisplatin (arm A)
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.
DRUGCisplatin (arm B)
Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.
Sponsors
Taiho Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
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: 1. Chemotherapy: 21 days 2. Radiotherapy: 21 days\* 3. 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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival, Safety | 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 | 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. |
Countries
Japan, South Korea, Taiwan
Participant flow
Recruitment details
375 patients were randomized to Arm A (189) or Arm B (186); of these, 364 patients(188 and 176, respectively) received study treatment. 11 patients (1 and 10, respectively) did not receive allocated intervention because of 'withdrew consent(1 and 6, respectively)' , 'ineligible criteria(3 in Arm B)', or 'investigator's discretion(1 in Arm B)'.
Participants by arm
| Arm | Count |
|---|---|
| S-1 + Cisplatin (Arm A) 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. | 188 |
| Cisplatin (Arm B) Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks. | 174 |
| Total | 362 |
Baseline characteristics
| Characteristic | S-1 + Cisplatin (Arm A) | Cisplatin (Arm B) | Total |
|---|---|---|---|
| Age, Continuous | 55 years | 52.5 years | 54 years |
| Region of Enrollment Japan | 110 participants | 105 participants | 215 participants |
| Region of Enrollment South Korea | 52 participants | 49 participants | 101 participants |
| Region of Enrollment Taiwan | 26 participants | 20 participants | 46 participants |
| Sex: Female, Male Female | 188 Participants | 174 Participants | 362 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 188 | 3 / 175 |
| other Total, other adverse events | 188 / 188 | 172 / 175 |
| serious Total, serious adverse events | 72 / 188 | 34 / 175 |
Outcome results
Primary
Overall Survival
Time frame: 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
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S-1 + Cisplatin (Arm A) | Overall Survival | 21.9 months |
| Cisplatin (Arm B) | Overall Survival | 19.5 months |
p-value: 0.12595% CI: [0.67, 1.05]Log Rank
Secondary
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.
Time frame: 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
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S-1 + Cisplatin (Arm A) | Progression Free Survival, Safety | 7.3 months |
| Cisplatin (Arm B) | Progression Free Survival, Safety | 4.9 months |
p-value: <0.00195% CI: [0.48, 0.8]Log Rank