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

NCT02965248 | Unknown Phase 3 DMC

• 1 other identifier: 1608163-15
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

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

Conditions

Locally Advanced Colorectal Cancer

Keywords

Locally advanced colorectal cancer; Hyperthermic intraperitoneal chemotherapy

Outcome Measures

Primary Outcomes (1)

• peritoneal metastasis rate

  3 years

Secondary Outcomes (5)

• 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

Study Arms (3)

Arm A

ACTIVE COMPARATOR

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.

Drug: Standard adjuvant systemic chemotherapy

Arm B

EXPERIMENTAL

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.

Drug: Standard adjuvant systemic chemotherapy; Procedure: Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed

Arm C

EXPERIMENTAL

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)

Drug: Standard adjuvant systemic chemotherapy; Procedure: Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin

Interventions

Standard adjuvant systemic chemotherapy DRUG

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.

Also known as: adjuvant oxaliplatin, 5-FU, and leucovorin calcium (mFOLFOX6), adjuvant oxaliplatin and capecitabine (CapeOx), adjuvant 5-FU and leucovorin calcium (sLV5FU2), adjuvant capecitabine (Cape)

Arm A; Arm B; Arm C

Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed PROCEDURE

Raltitrexed (3 mg/m2) is added to the perfusate after attaining 42 degrees of inflow temperature and last for 60 minutes.

Also known as: Intraperitoneal raltitrexed 3 mg/m2

Arm B

Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin PROCEDURE

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.

Also known as: I.V. leucovorin calcium 20 mg/m2, I.V. 5-FU 400 mg/m2, Intraperitoneal oxaliplatin 130 mg/m2

Arm C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

Fluorouracil; Leucovorin; Capecitabine; Hyperthermic Intraperitoneal Chemotherapy

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced

Study Officials

• Guoxiang Cai, M.D. Ph.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 11, 2016
• First Posted: November 16, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2023
• Last Updated: June 19, 2018

Record last verified: 2018-06

Locations

CN (1)