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

Locally Advanced Colorectal Cancer Clinical Trial

Official title:

Multicenter, Randomized Controlled Trial 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 (APEC Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02965248
• Other study ID #: 1608163-15
• Status: Recruiting
• Phase: Phase 3
• Start date: November 2016
• Est. completion date: November 2023

Study information

• Verified date: June 2018
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 147
• Est. completion date: November 2023
• Est. primary completion date: November 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Fever
• Locally Advanced Colorectal Cancer

Intervention

Drug:
• Standard adjuvant systemic chemotherapy
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.

Procedure:
• Hyperthermic 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.
• Hyperthermic 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.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	peritoneal metastasis rate		3 years
Secondary	liver metastasis rate		3 years
Secondary	disease free survival		3 years
Secondary	overall survival		5 years
Secondary	quality of life questionnaire		6 months
Secondary	Toxicity by NCI CTCAE v.4.0		5 years