Locally Advanced Colorectal Cancer
Conditions
Keywords
Locally advanced colorectal cancer, Hyperthermic intraperitoneal chemotherapy
Brief summary
This study is designed to evaluate the efficacy and safety of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed or oxaliplatin versus no HIPEC in locally advanced colorectal cancer
Detailed description
Peritoneum is one of the common sites of metastasis in advanced stage colorectal cancer patients, resulting in a poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is effective to colorectal peritoneal metastasis and may play a significant role in reducing the risk of metachronous peritoneal metastasis among patients with locally advanced colorectal cancer. Oxaliplatin is routinely used for HIPEC in the Europe and Raltitrexed may be another ideal drug for HIPEC. The present phase II multicenter, randomized controlled trial is designed to evaluate the efficacy and safety of adjuvant HIPEC with raltitrexed or oxaliplatin versus no HIPEC in locally advanced colorectal cancer.
Interventions
Patients undergo radical surgery with standard adjuvant systemic chemotherapy (mFOLFOX6/CapeOx/sLV5FU2/Cape). mFOLFOX6: oxaliplatin 85 mg/m2 IV d1 + leucovorin calcium 400 mg/m2 IV d1 + 5-FU 400 mg/m2 IV bolus d1 + 5-FU 2400 mg/m2 continuous IV over 46-48 hours d1-2. Repeat every two weeks for twelve cycles. CapeOx: oxaliplatin 130 mg/m2 IV d1 + capecitabine 1000mg/m2 po bid d1-14. Repeat every three weeks for eight cycles. sLV5FU2: leucovorin calcium 400 mg/m2 IV d1 + 5-FU 400 mg/m2 IV bolus d1 + 5-FU 2400 mg/m2 IV over 46-48 hours d1-2. Repeat every two weeks for twelve cycles. Cape: capecitabine 1000mg/m2 po bid d1-14. Repeat every three weeks for eight cycles.
PROCEDUREHyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed
Raltitrexed (3 mg/m2) is added to the perfusate after attaining 42 degrees of inflow temperature and last for 60 minutes.
PROCEDUREHyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin
Before the beginning of HIPEC, 5-FU 400 mg/m2 and leucovorin calcium 20 mg/m2 will be administered intravenously to potentiate oxaliplatin activity. Oxaliplatin (130 mg/m2) is added to the perfusate after attaining 42 degrees inflow temperature with a total of 30 minutes perfusion time.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Joined the study voluntarily and signed informed consent form * Eastern Cooperative Oncology Group performance status of 0 to 1 * Life expectancy of more than 5 years * Colorectal adenocarcinoma / mucinous adenocarcinoma / signet ring cell cancer confirmed by histopathology * Stage T4NanyM0 cancer; or stage T3NanyM0 mucinous adenocarcinoma / signet ring cell cancer / adenocarcinoma with partly mucinous adenocarcinoma or signet ring cell cancer * R0 resection of colorectal cancer * Neutrophils (ANC) ≥ 1.5×10\^9/L, Platelet count (Pt) ≥ 100× 10\^9/L, Hemoglobin (Hb) ≥ 80 g/L, Hepatic function: ALT and AST ≤ 2.5 times upper limit of normal (ULN) and TBIL ≤ 1.5 times ULN, Renal function: creatinine ≤ 1.5 times ULN * Use of an effective contraceptive for adults to prevent pregnancy
Exclusion criteria
* Rectal cancer below peritoneal reflection (≤ 8cm above the anal verge) * Other malignant tumors within the past 5 years, except for skin basal cell carcinoma, or cervical carcinoma in situ, who survived from radical treatment * Severe adhesion of peritoneal cavity impossible to separate * Abdominal infection * Allergic to raltitrexed, 5-FU, and oxaliplatin; Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency * Uncontrolled seizures or psychiatric diseases, loss of control over their own behavior * Drug addiction, Alcoholism or AIDS * Impossible to tolerate the operation due to severe cardiac, lung, and vascular diseases * Pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| peritoneal metastasis rate | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| liver metastasis rate | 3 years |
| disease free survival | 3 years |
| overall survival | 5 years |
| quality of life questionnaire | 6 months |
| Toxicity by NCI CTCAE v.4.0 | 5 years |
Countries
China
Outcome results
None listed