Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus no HIPEC in Locally Advanced Colorectal Cancer (APEC Study)

Phase 3

• Conditions: Locally Advanced Colorectal Cancer
• Interventions: Drug: Standard adjuvant systemic chemotherapy; Procedure: Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin; Procedure: Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed

• Registration Number: NCT02965248
• Lead Sponsor: Fudan University

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.

Study Timeline

• Study Start: 2016-11
• Study First Submitted: 2016-11-11
• Study First Submitted QC: 2016-11-11
• Study First Posted: 2016-11-16
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-16
• Last Update Posted: 2018-06-19
• Primary Completion: 2021-11
• Study Completion: 2023-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 147

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Standard adjuvant systemic chemotherapy	Patients undergo radical resection of colorectal cancer (open/laparoscopic) and receive standard adjuvant systemic chemotherapy comprising mFOLFOX6/CapeOx/sLV5FU2/Cape. Systemic chemotherapy will continue for 6 months. Patients also undergo HIPEC with raltitrexed (3mg/m2) intraperitoneally for 60 minutes during surgery or within 10 days after the operation.
Arm C	Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin	Patients undergo radical resection of colorectal cancer (open/laparoscopic) and receive standard adjuvant systemic chemotherapy comprising mFOLFOX6/CapeOx/sLV5FU2/Cape. Systemic chemotherapy will continue for 6 months. Patients also undergo HIPEC comprising oxaliplatin (130mg/m2) intraperitoneally during surgery and hyperthermia for 30 minutes, following leucovorin calcium (20mg/m2 intravenously) and 5-FU (400 mg/m2 intravenously)
Arm A	Standard adjuvant systemic chemotherapy	Patients undergo radical resection of colorectal cancer (open/laparoscopic) and receive standard adjuvant systemic chemotherapy comprising mFOLFOX6/CapeOx/sLV5FU2/Cape. Systemic chemotherapy will continue for 6 months.
Arm B	Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed	Patients undergo radical resection of colorectal cancer (open/laparoscopic) and receive standard adjuvant systemic chemotherapy comprising mFOLFOX6/CapeOx/sLV5FU2/Cape. Systemic chemotherapy will continue for 6 months. Patients also undergo HIPEC with raltitrexed (3mg/m2) intraperitoneally for 60 minutes during surgery or within 10 days after the operation.
Arm C	Standard adjuvant systemic chemotherapy	Patients undergo radical resection of colorectal cancer (open/laparoscopic) and receive standard adjuvant systemic chemotherapy comprising mFOLFOX6/CapeOx/sLV5FU2/Cape. Systemic chemotherapy will continue for 6 months. Patients also undergo HIPEC comprising oxaliplatin (130mg/m2) intraperitoneally during surgery and hyperthermia for 30 minutes, following leucovorin calcium (20mg/m2 intravenously) and 5-FU (400 mg/m2 intravenously)

Primary Outcome Measures

Name	Time	Method
peritoneal metastasis rate	3 years

Secondary Outcome Measures

Name	Time	Method
quality of life questionnaire	6 months
overall survival	5 years
liver metastasis rate	3 years
disease free survival	3 years
Toxicity by NCI CTCAE v.4.0	5 years

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China