Study of S-1 and Oxaliplatin (SOX) Versus Capecitabine and Oxaliplatin (COX) in Patients With Advanced Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT00677443
• Recruitment Status: Completed
• First Posted: May 14, 2008
• Last Update Posted: June 14, 2013
• Sponsor: Samsung Medical Center
• Collaborators: National Cancer Center, Korea; Seoul National University Bundang Hospital; Seoul National University Hospital; Gachon University Gil Medical Center; Yonsei University; Asan Medical Center; Chonnam National University Hospital
• Information provided by (Responsible Party): Young Suk Park, Samsung Medical Center

Tracking Information

• First Submitted Date: May 12, 2008
• First Posted Date: May 14, 2008
• Last Update Posted Date: June 14, 2013
• Study Start Date: June 2008
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 13, 2008): To compare the combination of S-1 and oxaliplatin to the combination of capecitabine and oxaliplatin in terms of progression free survival in patients previously untreated by systemic therapy for advanced or metastatic colorectal carcinoma. [ Time Frame: 9 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 13, 2008)

• To evaluate and compare the efficacy (overall survival and response rate) in the two treatment groups. [ Time Frame: 24 months ]
• To evaluate and compare the quality of life of the patients and safety profiles of the two treatment groups. [ Time Frame: 24 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of S-1 and Oxaliplatin (SOX) Versus Capecitabine and Oxaliplatin (COX) in Patients With Advanced Colorectal Cancer
• Official Title: A Randomized Phase III Study of SOX vs. COX in Patients With Advanced Colorectal Cancer

Brief Summary

Primary objective :

To compare the combination of S-1 and oxaliplatin(SOX) to the combination of capecitabine and oxaliplatin(COX) therapy for advanced or metastatic colorectal carcinoma.

Secondary objectives :

1. To evaluate and compare the efficacy (overall survival and response rate) in the two treatment groups.
2. To evaluate and compare the quality of life of the patients and safety profiles of the two treatment groups.

Detailed Description

• The urgent need for new effective therapy with better safety profile for metastatic colorectal cancer patients and promising results observed so far in trials with S-1 combined with oxaliplatin in gastrointestinal cancer including colorectal cancer strongly warrants the comparison of S-1 combined with oxaliplatin to capecitabine combination with oxaliplatin acknowledged as a standard regimen in a first-line treatment for advanced colorectal cancer patients.
• Recently, a Phase I study was completed, indicating recommended dose as S-1 100 mg/m2/day1-14 and oxaliplatin (130 mg/m2/day1), repeated every 3 weeks. However, in the phase II study using the above recommended dose, delayed toxicities of thrombocytopenia and anemia were observed. These delayed toxicities were also reported in a phase II study using S-1 90 mg/m2/day plus oxaliplatin 130 mg/m2/day1 in advanced gastric cancer. At 2007 GI ASCO, the interim data of S-1(80 mg/m2/day1-14) plus oxaliplatin (130 mg/m2/day1) combination, repeated every 3 weeks, was presented, showing promising antitumor activity with favourable safety profile. Among 18 patients, there were only two patients with Grade 3 thrombocytopenia and one with Grade 3 neutropenia. Response rate was 57.1 % and disease control rate was 92.9 %. Considering these results and Japanese data which showed that enhanced efficacy was not observed with S-1 over 90 mg/m2/day and oxaliplatin combination, S-1 80 mg/m2/day 1-14 and oxaliplatin 130 mg/m2/D1, repeated every 3 weeks, will be tested in this study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: S-1 & Oxaliplatin
  S-1 and Oxaliplatin : S-1 80 mg/m2/day, D1-14 Oxaliplatin, 130 mg/m2/day, D1 Repeated every 3 weeks
  Other Name: S-1 and Oxaliplatin
• Drug: Capecitabine & Oxaliplatin
  COX : Capecitabine 1000 mg/m2/day, D1-14 Oxaliplatin, 130 mg/m2/day, D1 Repeated every 3 weeks
  Other Name: Capecitabine and Oxaliplatin

Study Arms

• Experimental: S-1 and Oxaliplatin

  S-1 and Oxaliplatin

  S-1 : 80 mg/m2/day D1-14 Oxaliplatin : 130 mg/m2/day D1 Repeated every 3 weeks

  Intervention: Drug: S-1 & Oxaliplatin
• Active Comparator: Capecitabine and Oxaliplatin
  Capecitabine and Oxaliplatin
  Intervention: Drug: Capecitabine & Oxaliplatin

Publications *

• Kim ST, Hong YS, Lim HY, Lee J, Kim TW, Kim KP, Kim SY, Baek JY, Kim JH, Lee KW, Chung IJ, Cho SH, Lee KH, Shin SJ, Kang HJ, Shin DB, Lee JW, Jo SJ, Park YS. S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: updated results from a phase 3 trial. BMC Cancer. 2014 Nov 26;14:883. doi: 10.1186/1471-2407-14-883.
• Hong YS, Park YS, Lim HY, Lee J, Kim TW, Kim KP, Kim SY, Baek JY, Kim JH, Lee KW, Chung IJ, Cho SH, Lee KH, Shin SJ, Kang HJ, Shin DB, Jo SJ, Lee JW. S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial. Lancet Oncol. 2012 Nov;13(11):1125-32. doi: 10.1016/S1470-2045(12)70363-7. Epub 2012 Oct 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 2, 2008): 344
• Original Estimated Enrollment (submitted: May 13, 2008): 298
• Actual Study Completion Date: January 2011
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically documented colorectal adenocarcinoma
• Age over 18 years old
• Performance status (ECOG scale): 0-2
• Measurable or evaluable disease
• Patients can take food and drugs orally
• Adequate organ functions
• Life expectancy ≥ 3 months
• Patients should sign a written informed consent before study entry

Exclusion Criteria:

• Tumor type other than adenocarcinoma
• Second primary malignancy
• Prior systemic therapy (for instance, cytotoxic chemotherapy or active/passive immunotherapy) for advanced or metastatic colorectal cancer
• Adjuvant or neo-adjuvant treatment for non-metastatic (M0) disease has been completed within 6 months prior to initiation of study treatment.
• Prior radiotherapy was administered to target lesions selected for this study, or radiotherapy to the non-target lesions has been completed within 4 weeks before randomization.
• Presence of CNS metastasis
• Obvious peritoneal seeding or bowel obstruction disturbing oral intake
• Symptomatic peripheral neuropathy
• Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery. The patient received curative operation or RFA for metastatic disease.
• Serious illness or medical conditions
• Receiving a concomitant treatment with drugs interacting with S-1, capecitabine or oxaliplatin, as follows;flucytosine, a fluorinated pyrimidine antifungal agent phenytoin warfarin etc.
• Received any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug.
• Pregnant or lactating woman
• Women of child bearing potential not using a contraceptive method
• Sexually active fertile men not using effective birth control during medication of study drug and up to 6 months after completion of study drug if their partners are women of child-bearing potential
• Any patients judged by the investigator to be unfit to participate in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 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: Korea, Republic of

Administrative Information

• NCT Number: NCT00677443
• Other Study ID Numbers: 2008-03-012
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Young Suk Park, Samsung Medical Center
• Original Responsible Party: Young Suk Park M.D.,Ph.D. Professor, Samsung Medical Center
• Current Study Sponsor: Samsung Medical Center
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Center, Korea
• Seoul National University Bundang Hospital
• Seoul National University Hospital
• Gachon University Gil Medical Center
• Yonsei University
• Asan Medical Center
• Chonnam National University Hospital

Investigators

• Study Chair: Young Suk Park, M.D.,Ph.D.; Samsung Medical Center, Seoul, Korea
• Principal Investigator: Hye Jin Kang, M.D.,Ph.D.; Korea Cancer Center Hospital , Seoul, Korea
• Principal Investigator: Jee Hyun Kim, M.D.,Ph.D.; Seoul National University Bundang Hospital, Gyeonggi, Korea
• Principal Investigator: Tae Won Kim, M.D.,Ph.D.; Asan Medical Center, Seoul, Korea
• Principal Investigator: Tae-Yoo Kim, M.D.,Ph.D.; Seoul National University Hospital , Seoul, Korea
• Principal Investigator: Dong Bok Shin, M.D.,Ph.D.; Gil Medical Center, Gyeonggi, Korea
• Principal Investigator: Joong Bae Ahn, M.D.,Ph.D.; Yonsei Medical Center, Severance Hospital, Seoul, Korea
• Principal Investigator: Kyung Hee Lee, M.D.,Ph.D.; Yeungnam University College of Medicine , Daegu, Korea
• Principal Investigator: Namsu Lee, M.D.,Ph.D.; Soon Chun Hyang University Hospital , Seoul, Korea
• Principal Investigator: Ik-Joo Chung, M.D.,Ph.D.; Chonnam National University Hwasun Hospital, Jeollanamdo, Korea
• Principal Investigator: Yong Sang Hong, M.D.,Ph.D.; National Cancer Center, Gyeonggi, Korea

• PRS Account: Samsung Medical Center
• Verification Date: June 2013