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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Taiho Pharmaceutical Co., Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cervical Cancer
Interventions Drug: S-1 + Cisplatin (arm A)
Drug: Cisplatin (arm B)
Enrollment 375
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)'.
Pre-assignment Details  
Arm/Group Title S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Hide Arm/Group Description 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. Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.
Period Title: Overall Study
Started 188 176
Completed 188 176
Not Completed 0 0
Arm/Group Title S-1 + Cisplatin (Arm A) Cisplatin (Arm B) Total
Hide Arm/Group Description 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. Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks. Total of all reporting groups
Overall Number of Baseline Participants 188 174 362
Hide Baseline Analysis Population Description
A total of 364 (188 in Arm A; 176 in Arm B) received study treatment. Two patients in Arm B were excluded in the efficacy analysis, because of insufficient informed consent, and missing efficacy data.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 188 participants 174 participants 362 participants
55
(27 to 84)
52.5
(28 to 81)
54
(27 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 188 participants 174 participants 362 participants
Female
188
 100.0%
174
 100.0%
362
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 188 participants 174 participants 362 participants
South Korea 52 49 101
Japan 110 105 215
Taiwan 26 20 46
1.Primary Outcome
Title Overall Survival
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Hide Arm/Group Description:
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.
Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.
Overall Number of Participants Analyzed 188 174
Median (95% Confidence Interval)
Unit of Measure: months
21.9
(18.6 to 25.8)
19.5
(17.0 to 24.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-1 + Cisplatin (Arm A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.125
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.67 to 1.05
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival, Safety
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Hide Arm/Group Description:
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.
Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.
Overall Number of Participants Analyzed 188 174
Median (95% Confidence Interval)
Unit of Measure: months
7.3
(6.7 to 8.1)
4.9
(4.4 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-1 + Cisplatin (Arm A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.48 to 0.80
Estimation Comments [Not Specified]
Time Frame From the date of the first treatment to 30 days after the last treatment
Adverse Event Reporting Description A total of 364 (188 in Arm A; 176 in Arm B) received study treatment. One patient in Arm B were excluded in the safety analysis, because of insufficient informed consent.
 
Arm/Group Title S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Hide Arm/Group Description 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. Cisplatin 50 mg/m2 will be administered intravenously (IV) on Day 1, repeated every 3 weeks.
All-Cause Mortality
S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   7/188 (3.72%)   3/175 (1.71%) 
Hide Serious Adverse Events
S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   72/188 (38.30%)   34/175 (19.43%) 
Blood and lymphatic system disorders     
Disseminated intravascular coagulation * 1  2/188 (1.06%)  0/175 (0.00%) 
Febrile neutropenia * 1  3/188 (1.60%)  0/175 (0.00%) 
Cardiac disorders     
Myocardial ischaemia * 1  1/188 (0.53%)  1/175 (0.57%) 
Ear and labyrinth disorders     
Deafness * 1  1/188 (0.53%)  0/175 (0.00%) 
Eye disorders     
Glaucoma * 1  1/188 (0.53%)  0/175 (0.00%) 
Gastrointestinal disorders     
Abdominal distension * 1  0/188 (0.00%)  1/175 (0.57%) 
Abdominal pain * 1  3/188 (1.60%)  2/175 (1.14%) 
Abdominal pain upper * 1  1/188 (0.53%)  1/175 (0.57%) 
Ascities * 1  0/188 (0.00%)  2/175 (1.14%) 
Diarrhoea * 1  9/188 (4.79%)  0/175 (0.00%) 
Gastric perforation * 1  1/188 (0.53%)  0/175 (0.00%) 
Gastritis * 1  0/188 (0.00%)  1/175 (0.57%) 
Illeus * 1  2/188 (1.06%)  1/175 (0.57%) 
Nausea * 1  2/188 (1.06%)  2/175 (1.14%) 
Peritoneal haemorrhage * 1  1/188 (0.53%)  0/175 (0.00%) 
Rectal haemorrhage * 1  0/188 (0.00%)  2/175 (1.14%) 
Rectal stenosis * 1  0/188 (0.00%)  1/175 (0.57%) 
Small intestinal obstruction * 1  3/188 (1.60%)  2/175 (1.14%) 
Stomatitis * 1  1/188 (0.53%)  0/175 (0.00%) 
Vomiting * 1  4/188 (2.13%)  0/175 (0.00%) 
Subileus * 1  1/188 (0.53%)  1/175 (0.57%) 
Lower gastrointestinal haemorrhage * 1  2/188 (1.06%)  0/175 (0.00%) 
Intra-abdominal haemorrhage * 1  1/188 (0.53%)  0/175 (0.00%) 
General disorders     
Fatigue * 1  3/188 (1.60%)  0/175 (0.00%) 
Oedema peripheral * 1  2/188 (1.06%)  0/175 (0.00%) 
Pyrexia * 1  4/188 (2.13%)  0/175 (0.00%) 
Disease progression * 1  0/188 (0.00%)  1/175 (0.57%) 
Infections and infestations     
Gastroenteritis * 1  1/188 (0.53%)  0/175 (0.00%) 
Herpes zoster * 1  1/188 (0.53%)  0/175 (0.00%) 
Infectious colitis * 1  1/188 (0.53%)  0/175 (0.00%) 
Infective myositis * 1  1/188 (0.53%)  0/175 (0.00%) 
Peritonitis * 1  1/188 (0.53%)  0/175 (0.00%) 
Salpingitis * 1  1/188 (0.53%)  0/175 (0.00%) 
Sepsis * 1  1/188 (0.53%)  1/175 (0.57%) 
Skin infection * 1  2/188 (1.06%)  0/175 (0.00%) 
Upper respiratory tract infection * 1  2/188 (1.06%)  0/175 (0.00%) 
Urinary tract infection * 1  5/188 (2.66%)  4/175 (2.29%) 
Ureteritis * 1  0/188 (0.00%)  1/175 (0.57%) 
Uterine infection * 1  1/188 (0.53%)  0/175 (0.00%) 
Device related infection * 1  0/188 (0.00%)  1/175 (0.57%) 
Injury, poisoning and procedural complications     
Fracture * 1  1/188 (0.53%)  0/175 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/188 (0.53%)  1/175 (0.57%) 
Aspartate aminotransferase increased * 1  1/188 (0.53%)  1/175 (0.57%) 
Blood albumin decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Blood calcium decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Blood glucose decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Blood magnesium decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Blood potassium decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Blood sodium decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Blood uric acid decreased * 1  1/188 (0.53%)  0/175 (0.00%) 
Haemoglobin decreased * 1  10/188 (5.32%)  5/175 (2.86%) 
Neutrophil count decreased * 1  12/188 (6.38%)  0/175 (0.00%) 
Platelet count decreased * 1  5/188 (2.66%)  0/175 (0.00%) 
White blood cell count decreased * 1  2/188 (1.06%)  0/175 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/188 (1.06%)  0/175 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  2/188 (1.06%)  1/175 (0.57%) 
Pain in extremity * 1  1/188 (0.53%)  0/175 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Thyroid cancer * 1  0/188 (0.00%)  1/175 (0.57%) 
Nervous system disorders     
Extrapyramidal disorder * 1  1/188 (0.53%)  0/175 (0.00%) 
Peripheral motor neuropathy * 1  1/188 (0.53%)  0/175 (0.00%) 
VIIth nerve paralysis * 1  1/188 (0.53%)  0/175 (0.00%) 
Renal and urinary disorders     
Hydroneprosis * 1  2/188 (1.06%)  2/175 (1.14%) 
Obstructive uropathy * 1  0/188 (0.00%)  1/175 (0.57%) 
Renal failure * 1  3/188 (1.60%)  2/175 (1.14%) 
Ureteric obstruction * 1  5/188 (2.66%)  2/175 (1.14%) 
Ureteric stenosis * 1  1/188 (0.53%)  1/175 (0.57%) 
Urinary retention * 1  0/188 (0.00%)  1/175 (0.57%) 
Reproductive system and breast disorders     
Breast engorgement * 1  0/188 (0.00%)  1/175 (0.57%) 
Uterine haemorrhage * 1  0/188 (0.00%)  2/175 (1.14%) 
Vaginal haemorrhage * 1  0/188 (0.00%)  1/175 (0.57%) 
Vaginal fistula * 1  0/188 (0.00%)  2/175 (1.14%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  0/188 (0.00%)  2/175 (1.14%) 
Pleural effusion * 1  1/188 (0.53%)  0/175 (0.00%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer * 1  0/188 (0.00%)  1/175 (0.57%) 
Urticaria * 1  1/188 (0.53%)  0/175 (0.00%) 
Exfoliative rash * 1  1/188 (0.53%)  0/175 (0.00%) 
Vascular disorders     
Thrombosis * 1  10/188 (5.32%)  2/175 (1.14%) 
1
Term from vocabulary, CTCAE (3.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
S-1 + Cisplatin (Arm A) Cisplatin (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   188/188 (100.00%)   172/175 (98.29%) 
Gastrointestinal disorders     
Abdominal distension * 1  12/188 (6.38%)  5/175 (2.86%) 
Abdominal pain * 1  29/188 (15.43%)  26/175 (14.86%) 
Abdominal pain upper * 1  24/188 (12.77%)  9/175 (5.14%) 
Constipation * 1  61/188 (32.45%)  48/175 (27.43%) 
Diarrhoea * 1  94/188 (50.00%)  51/175 (29.14%) 
Dyspesia * 1  21/188 (11.17%)  12/175 (6.86%) 
Gastritis * 1  19/188 (10.11%)  10/175 (5.71%) 
Nausea * 1  153/188 (81.38%)  134/175 (76.57%) 
Stomatitis * 1  59/188 (31.38%)  16/175 (9.14%) 
Vomiting * 1  103/188 (54.79%)  71/175 (40.57%) 
Fatigue * 1  109/188 (57.98%)  79/175 (45.14%) 
General disorders     
Influenza like illness * 1  29/188 (15.43%)  17/175 (9.71%) 
Oedema peripheral * 1  41/188 (21.81%)  16/175 (9.14%) 
Pyrexia * 1  38/188 (20.21%)  20/175 (11.43%) 
Localised oedema * 1  20/188 (10.64%)  15/175 (8.57%) 
Immune system disorders     
Hypersensitivity * 1  10/188 (5.32%)  9/175 (5.14%) 
Infections and infestations     
Cystitis * 1  12/188 (6.38%)  9/175 (5.14%) 
Upper respiratory tract infection * 1  12/188 (6.38%)  6/175 (3.43%) 
Urinary tract infection * 1  17/188 (9.04%)  12/175 (6.86%) 
Investigations     
Alanine aminotransferase increased * 1  38/188 (20.21%)  23/175 (13.14%) 
Aspartate aminotransferase increased * 1  33/188 (17.55%)  15/175 (8.57%) 
Blood albumin decreased * 1  46/188 (24.47%)  23/175 (13.14%) 
Blood bilirubin decreased * 1  21/188 (11.17%)  3/175 (1.71%) 
Blood calcium decreased * 1  18/188 (9.57%)  6/175 (3.43%) 
Blood creatinine increased * 1  38/188 (20.21%)  39/175 (22.29%) 
Blood potassium decreased * 1  39/188 (20.74%)  9/175 (5.14%) 
Blood sodium decreased * 1  30/188 (15.96%)  15/175 (8.57%) 
Haemoglobin decreased * 1  147/188 (78.19%)  87/175 (49.71%) 
Lymphocyte count decreased * 1  21/188 (11.17%)  10/175 (5.71%) 
Neutrophil count decreased * 1  148/188 (78.72%)  65/175 (37.14%) 
Platelet count decreased * 1  90/188 (47.87%)  26/175 (14.86%) 
Weight decreased * 1  38/188 (20.21%)  10/175 (5.71%) 
Weight increased * 1  11/188 (5.85%)  10/175 (5.71%) 
White blood cell count decreased * 1  92/188 (48.94%)  52/175 (29.71%) 
Protein urine present * 1  29/188 (15.43%)  13/175 (7.43%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  141/188 (75.00%)  105/175 (60.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  26/188 (13.83%)  12/175 (6.86%) 
Muscular weakness * 1  16/188 (8.51%)  9/175 (5.14%) 
Pain in extremity * 1  9/188 (4.79%)  10/175 (5.71%) 
Nervous system disorders     
Dizziness * 1  37/188 (19.68%)  15/175 (8.57%) 
Dysgeusia * 1  34/188 (18.09%)  12/175 (6.86%) 
Headache * 1  32/188 (17.02%)  31/175 (17.71%) 
Peripheral sensory neuropathy * 1  39/188 (20.74%)  22/175 (12.57%) 
Psychiatric disorders     
Insomnia * 1  28/188 (14.89%)  21/175 (12.00%) 
Renal and urinary disorders     
Ureteric obstruction * 1  10/188 (5.32%)  5/175 (2.86%) 
Reproductive system and breast disorders     
Vaginal haemorrhage * 1  11/188 (5.85%)  5/175 (2.86%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  24/188 (12.77%)  12/175 (6.86%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  15/188 (7.98%)  2/175 (1.14%) 
Pruritus * 1  21/188 (11.17%)  7/175 (4.00%) 
Skin hyperpigmentation * 1  48/188 (25.53%)  2/175 (1.14%) 
Exfoliative rash * 1  36/188 (19.15%)  18/175 (10.29%) 
Vascular disorders     
Thrombosis * 1  14/188 (7.45%)  4/175 (2.29%) 
1
Term from vocabulary, CTCAE (3.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Taiho Pharmaceutical Co., Ltd.
Organization: Clinical Trial Registration Contact
EMail: toiawase@taiho.co.jp
Layout table for additonal information
Responsible Party: Taiho Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT00770874    
Other Study ID Numbers: 10020380
First Submitted: October 9, 2008
First Posted: October 10, 2008
Results First Submitted: October 22, 2018
Results First Posted: June 21, 2019
Last Update Posted: June 21, 2019