Clinical trial NCT03125980: Perioperative Versus Postoperative CapOX Chemotherapy for Locally Advanced Colon Cancer
Official title: Perioperative CapeOX Chemotherapy Versus Postoperative Chemotherapy for Locally Advanced Resectable Colon Cancer: An Open Label Randomized Controlled Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Locally Advanced Colon Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2017-04-24
Enrollment: 1370
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Adjuvant chemotherapy has been widely adopted worldwide for locally advanced colon cancer. However, more and more studies have found better efficacy and potential advantages of perioperative or neoadjuvant chemotherapy. The sooner the systemic chemotherapy is received, the better suppression it has on activity of tumor growth factors. Pre-operative chemotherapy may eliminate tiny metastases. It may also shrink the invasion of tumor before surgery, and thus reducing operational trauma and expediting recovery. With advances in radiology and tomography, staging before surgery is accurate enough to identify risks and prognosis for patients. The phase II trial conducted by our department has yielded encouraging results (N=47, CapeOX regimen, clinicaltrials.gov NCT02415829): after the neoadjuvant chemotherapy, no subject had disease progression, 68.1% subjects reached complete or partial response. Besides, the toxicity of neoadjuvant CapeOX chemotherapy was acceptable. The present randomized controlled phase III trial will be conducted to further compare efficacy and safety of the neoadjuvant and adjuvant CapeOX chemotherapy for patients with locally advanced resectable colon cancer in China. This study may have two periods, each will last for approximately 5 years. After the first period (n=994), if the results of the test group are better than the control group, the study will be terminated. Otherwise, the study will enter into period 2 (n=376) through selecting out genetically sensitive subjects and repeating the same trial process as period 1.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2;
* Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Neutrophil count≥1.5×109/L, Platelet count≥100×109/L, Hemoglobin≥80g/L, Serum bilirubin≤24umol/L, Alanine aminotransferase and aspartate aminotransferase ≤ 60×IU/L, Serum creatinine≤110 umol/L;
* No current pregnancy or breast-feeding, and subjects at childbearing age shall take method of contraception ;
* Be in a condition to receive a surgery/procedure;
* No second tumor at present or in the past 5 years, except skin basal cell carcinoma, skin squamous cell carcinoma, or any in situ cancer;
* No previous systemic chemotherapy for treating colon cancer;
* No other chemotherapy at the same time;
* Expected lifetime longer than three months;
* Be willing and able to understand the study and to provide written informed consent.

Exclusion Criteria:

* End-stage cachexia patients;
* Cardiopulmonary dysfunction or liver and kidney dysfunction, and unable to tolerate CapeOX chemotherapy;
* Metastatic carcinoma;
* Moderate or above anemia caused by serious local tumor bleeding;
* Incomplete or complete intestinal obstruction;
* Known to be allergic to oxaliplatin or capecitabine;
* Active hepatitis, severe coagulation disorder patients;
* Pregnant or lactating women; or women who have fertility but have not taken at taken adequate contraceptive measures;
* Known to have deficient dihydropyrimidine dehydrogenase (DPD)；
* Have vital organ failure or other severe diseases, including but not limited to coronary heart disease, cardiovascular diseases, or myocardial infarction within 12 months before being included; severe neurological or psychiatric history；severe infection; active disseminated intravascular coagulation;
* Unable or unwilling to abide by the study plan.

Primary outcomes:
measure: 3-year disease free survival
timeFrame: 3 years
Secondary outcomes:
measure: R0 resection rate
timeFrame: From the date of randomization until the date of the last patient receiving surgery, assessed up to 40 months
measure: Post-operative TRG staging
timeFrame: From the date of randomization until the date of the last patients receiving surgery, assessed up to 40 months
measure: Overall survival (OS)
timeFrame: 5 years
measure: Relapse-free survival (RFS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Colorectal Surgery Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Department of Colorectal Surgery Fudan University Shanghai Cancer Center
name: Ye Xu, M.D
role: STUDY_DIRECTOR
References:
citation: Liu F, Tong T, Huang D, Yuan W, Li D, Lin J, Cai S, Xu Y, Chen W, Sun Y, Zhuang J. CapeOX perioperative chemotherapy versus postoperative chemotherapy for locally advanced resectable colon cancer: protocol for a two-period randomised controlled phase III trial. BMJ Open. 2019 Jan 29;9(1):e017637. doi: 10.1136/bmjopen-2017-017637.