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

Condition(s) targeted: Colorectal Cancer

Intervention: S-1 & Oxaliplatin (Drug); Capecitabine & Oxaliplatin (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Samsung Medical Center

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

Overall contact:
Young Suk Park, M.D.,Ph.D., Phone: 82-2-3410-3459, Email: pys27hmo@skku.edu

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.

Official title: A Randomized Phase III Study of SOX vs. COX in Patients With Advanced Colorectal Cancer

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

To evaluate and compare the efficacy (overall survival and response rate) in the two treatment groups.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Young Suk Park, M.D.,Ph.D., Phone: 82-2-3410-3459, Email: pys27hmo@skku.edu

Yeungnam University, Daegu 705-717, Korea, Republic of; Recruiting
Kyung Hee Lee, M.D.,Ph.D., Phone: 82-53-620-3845, Email: lkhee@med.yu.ac.kr
Kyung Hee Lee, M.D.,Ph.D., Principal Investigator

Gachon University Gil Medical Center, Inchon, Korea, Republic of; Recruiting
Dong Bok Shin, M.D.,Ph.D., Email: dbs@gilhospital.com
Dong Bok Shin, M.D.,Ph.D., Principal Investigator

Korea Cancer Center Hospital, Seoul 139-706, Korea, Republic of; Recruiting
Hye Jin Kang, M.D.,Ph.D., Phone: 82-2-970-1289, Email: hyejin@kcch.re.kr
Hye Jin Kang, M.D.,Ph.D., Principal Investigator

Asan Medical Center, Seoul 138-736, Korea, Republic of; Recruiting
Tae Won Kim, M.D.,Ph.D., Phone: 82-2-3010-3910, Email: twkimmd@amc.seoul.kr
Tae Won Kim, M.D.,Ph.D., Principal Investigator

Soon Chun Hyang University Hospital, Seoul 140-743, Korea, Republic of; Recruiting
Namsu Lee, M.D.,Ph.D., Phone: 82-2-709-9483, Email: mdnslee@hosp.sch.ac.kr
Namsu Lee, M.D.,Ph.D., Principal Investigator

Seoul National University Hospital, Seoul, Korea, Republic of; Recruiting
Tae-Yoo Kim, M.D.,Ph.D., Email: kimty@snu.ac.kr
Tae-Yoo Kim, M.D.,Ph.D., Principal Investigator

Samsung Medical Center, Seoul 135-710, Korea, Republic of; Not yet recruiting
Young Suk Park, M.D.,Ph.D., Phone: 82-2-3410-3459, Email: pys27hmo@skku.edu
Se Hoon Park, M.D., Phone: 82-2-3410-1767, Email: hematoma@skku.edu
Young Suk Park, M.D.,Ph.D., Principal Investigator
Won Ki Kang, M.D.,Ph.D., Sub-Investigator
Ho Yeong Lim, M.D.,Ph.D., Sub-Investigator
Joon Oh Park, M.D.,Ph.D., Sub-Investigator
Jeeyun Lee, M.D.,Ph.D., Sub-Investigator
Se Hoon Park, M.D.,Ph.D., Sub-Investigator

Yonsei University, Seoul, Korea, Republic of; Recruiting
Joong Bae Ahn, M.D.,Ph.D., Email: vvswm513@yuhs.ac
Joong Bae Ahn, M.D.,Ph.D., Principal Investigator

National Cancer Center, Goyang, Gyeonggi 410-769, Korea, Republic of; Recruiting
Yong Sang Hong, M.D., Phone: 82-31-920-1893, Email: yshong@ncc.re.kr
Yong Sang Hong, M.D., Principal Investigator

Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea, Republic of; Recruiting
Jee Hyun Kim, Phone: M.D.,Ph.D., Email: jhkimmd@snu.ac.kr
Jee Hyun Kim, M.D.,Ph.D., Principal Investigator

Chonnam National University Hospital, Hwasun, Jeollanamdo 519-809, Korea, Republic of; Recruiting
Ik-Joo Chung, M.D.,Ph.D., Phone: 82-61-379-7632, Email: ijchung@jnu.ac.kr
Ik-Joo Chung, M.D.,Ph.D., Principal Investigator

Starting date: June 2008
Last updated: June 22, 2010