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

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: S-1 + Cisplatin (arm A); Drug: Cisplatin (arm B)

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
• Enrollment (Actual): 375
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka
    • Chikushimachi, Yanagawa, Fukuoka, Japan, 832-0077
      • Yanagawa Hospital
  • Tokyo
    • Ariake, Koto-ku, Tokyo, Japan, 135-8550
      • Cancer Institute Hospital
• Korea, Republic of
  • Seoul
    • Hwayang-dong, Gwangjin-gu, Seoul, Korea, Republic of, 143-729
      • Konkuk University Medical Center
• Taiwan
  • TaoYuan Hsien
    • Fu-Hsing Saint Kuei Shan Hsiang, TaoYuan Hsien, Taiwan, 33305
      • Chang Gung Medical Foundation- Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; S-1 + Cisplatin (arm A)	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.
Active Comparator: 2; Cisplatin (arm B)	Drug: Cisplatin (arm B); Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: Taiho Pharmaceutical Co., Ltd.
• 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

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: October 9, 2008
• First Submitted That Met QC Criteria: October 9, 2008
• First Posted (Estimate): October 10, 2008

Study Record Updates

• Last Update Posted (Actual): June 21, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: 10020380