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

Primary Purpose

Locally Advanced Colorectal Cancer

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Standard adjuvant systemic chemotherapy

Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed

Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin

About this trial

This is an interventional treatment trial for Locally Advanced Colorectal Cancer focused on measuring Locally advanced colorectal cancer, Hyperthermic intraperitoneal chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm C

Arm Description

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.

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)

Outcomes

Primary Outcome Measures

peritoneal metastasis rate

Secondary Outcome Measures

liver metastasis rate

disease free survival

overall survival

quality of life questionnaire

Toxicity by NCI CTCAE v.4.0

Full Information

NCT ID

NCT02965248

First Posted

November 11, 2016

Last Updated

June 16, 2018

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT02965248

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Recruiting

Study Start Date

November 2016 (undefined)

Primary Completion Date

November 2021 (Anticipated)

Study Completion Date

November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Advanced Colorectal Cancer

Keywords

Locally advanced colorectal cancer, Hyperthermic intraperitoneal chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

147 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

Arm Title

Arm B

Arm Type

Experimental

Arm Description

Arm Title

Arm C

Arm Type

Experimental

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

Standard adjuvant systemic chemotherapy

Other Intervention Name(s)

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

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed

Other Intervention Name(s)

Intraperitoneal raltitrexed 3 mg/m2

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin

Other Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

peritoneal metastasis rate

Time Frame

3 years

Secondary Outcome Measure Information:

Title

liver metastasis rate

Time Frame

3 years

Title

disease free survival

Time Frame

3 years

Title

overall survival

Time Frame

5 years

Title

quality of life questionnaire

Time Frame

6 months

Title

Toxicity by NCI CTCAE v.4.0

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Guoxiang Cai, M.D. Ph.D.

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Guoxiang Cai, M.D. Ph.D.

Phone

+86 13611831623

gxcai@fudan.edu.cn

12. IPD Sharing Statement

Learn more about this trial

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

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