Clinical trial NCT00677443: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: metastatic colorectal cancer
S-1
Capecitabine
Oxaliplatin
non-inferiority study
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Center, Korea
name: Seoul National University Bundang Hospital
name: Seoul National University Hospital
name: Gachon University Gil Medical Center
name: Yonsei University
name: Asan Medical Center
name: Chonnam National University Hospital
First posted: 2008-05-14
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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.
timeFrame: 9 months
Secondary outcomes:
measure: To evaluate and compare the efficacy (overall survival and response rate) in the two treatment groups.
timeFrame: 24 months
measure: To evaluate and compare the quality of life of the patients and safety profiles of the two treatment groups.
timeFrame: 24 months
Other outcomes:
Locations:
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Jeollanamdo
city: Daegu
country: Korea, Republic of
facility: Yeungnam University
city: Inchon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University
Study officials:
affiliation: Samsung Medical Center, Seoul, Korea
name: Young Suk Park, M.D.,Ph.D.
role: STUDY_CHAIR
affiliation: Korea Cancer Center Hospital , Seoul, Korea
name: Hye Jin Kang, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital, Gyeonggi, Korea
name: Jee Hyun Kim, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Asan Medical Center, Seoul, Korea
name: Tae Won Kim, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital , Seoul, Korea
name: Tae-Yoo Kim, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Gil Medical Center, Gyeonggi, Korea
name: Dong Bok Shin, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Yonsei Medical Center, Severance Hospital, Seoul, Korea
name: Joong Bae Ahn, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Yeungnam University College of Medicine , Daegu, Korea
name: Kyung Hee Lee, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Soon Chun Hyang University Hospital , Seoul, Korea
name: Namsu Lee, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Chonnam National University Hwasun Hospital, Jeollanamdo, Korea
name: Ik-Joo Chung, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Center, Gyeonggi, Korea
name: Yong Sang Hong, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.