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

June 16, 2018 updated by: Guoxiang Cai, Fudan University

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

147

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A
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

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.

Other Names:
  • adjuvant oxaliplatin, 5-FU, and leucovorin calcium (mFOLFOX6)
  • adjuvant oxaliplatin and capecitabine (CapeOx)
  • adjuvant 5-FU and leucovorin calcium (sLV5FU2)
  • adjuvant capecitabine (Cape)
Experimental: Arm B
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

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.

Other Names:
  • adjuvant oxaliplatin, 5-FU, and leucovorin calcium (mFOLFOX6)
  • adjuvant oxaliplatin and capecitabine (CapeOx)
  • adjuvant 5-FU and leucovorin calcium (sLV5FU2)
  • adjuvant capecitabine (Cape)
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.
Other Names:
  • Intraperitoneal raltitrexed 3 mg/m2
Experimental: Arm C
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

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.

Other Names:
  • adjuvant oxaliplatin, 5-FU, and leucovorin calcium (mFOLFOX6)
  • adjuvant oxaliplatin and capecitabine (CapeOx)
  • adjuvant 5-FU and leucovorin calcium (sLV5FU2)
  • adjuvant capecitabine (Cape)
Procedure: 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.
Other Names:
  • I.V. leucovorin calcium 20 mg/m2
  • I.V. 5-FU 400 mg/m2
  • Intraperitoneal oxaliplatin 130 mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
peritoneal metastasis rate
Time Frame: 3 years
3 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Guoxiang Cai, M.D. Ph.D., Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Anticipated)

November 1, 2021

Study Completion (Anticipated)

November 1, 2023

Study Registration Dates

First Submitted

November 11, 2016

First Submitted That Met QC Criteria

November 11, 2016

First Posted (Estimate)

November 16, 2016

Study Record Updates

Last Update Posted (Actual)

June 19, 2018

Last Update Submitted That Met QC Criteria

June 16, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1608163-15

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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