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

• ClinicalTrials.gov Identifier: NCT00770874
• Recruitment Status: Completed
• First Posted: October 10, 2008
• Results First Posted: June 21, 2019
• Last Update Posted: June 21, 2019
• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Taiho Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: October 9, 2008
• First Posted Date: October 10, 2008
• Results First Submitted Date: October 22, 2018
• Results First Posted Date: June 21, 2019
• Last Update Posted Date: June 21, 2019
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 18, 2019): 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 ]
• Original Primary Outcome Measures (submitted: October 9, 2008): Overall survival [ Time Frame: Once every 3 months ]

Current Secondary Outcome Measures (submitted: March 18, 2019)

Progression Free Survival, Safety [ 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 ]

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.

• Original Secondary Outcome Measures (submitted: October 9, 2008): Progression free survival, Overall response rate, safety [ Time Frame: Once every 3 months (PFS), Once every 6 weeks (ORR), anytime (safety) ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of S-1 + Cisplatin vs Cisplatin in Cervical Cancer
• Official Title: Phase III Study of S-1 + Cisplatin Compared With Single-agent Cisplatin in Stage IVB, Recurrent, or Persistent Carcinoma of the Cervix
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cervical Cancer

Intervention

• Drug: 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.
• Drug: Cisplatin (arm B)
  Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.

Study Arms

• Experimental: 1
  S-1 + Cisplatin (arm A)
  Intervention: Drug: S-1 + Cisplatin (arm A)
• Active Comparator: 2
  Cisplatin (arm B)
  Intervention: Drug: Cisplatin (arm B)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 21, 2016): 375
• Original Estimated Enrollment (submitted: October 9, 2008): 360
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, Korea, Republic of, Taiwan

Administrative Information

• NCT Number: NCT00770874
• Other Study ID Numbers: 10020380
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Taiho Pharmaceutical Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taiho Pharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Ken Takizawa, MD; Cancer Institute Hospital
• Study Chair: Toshiharu Kamura, MD; Yanagawa Hospital
• Study Chair: Ting-Chang Chang, MD; Chang Gung Memorial Hospital
• Study Chair: Soon-Beom Kang, MD; Konkuk University Medical Center

• PRS Account: Taiho Pharmaceutical Co., Ltd.
• Verification Date: March 2019