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

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ClinicalTrials.gov Identifier: NCT02965248
Recruitment Status : Recruiting
First Posted : November 16, 2016
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Guoxiang Cai, Fudan University

Tracking Information
First Submitted Date  ICMJE November 11, 2016
First Posted Date  ICMJE November 16, 2016
Last Update Posted Date June 19, 2018
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2016)
peritoneal metastasis rate [ Time Frame: 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2016)
  • liver metastasis rate [ Time Frame: 3 years ]
  • disease free survival [ Time Frame: 3 years ]
  • overall survival [ Time Frame: 5 years ]
  • quality of life questionnaire [ Time Frame: 6 months ]
  • Toxicity by NCI CTCAE v.4.0 [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus no HIPEC in Locally Advanced Colorectal Cancer (APEC Study)
Official Title  ICMJE 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)
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced Colorectal Cancer
Intervention  ICMJE
  • 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 Name: Intraperitoneal raltitrexed 3 mg/m2
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Standard adjuvant systemic chemotherapy
  • 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.
    Interventions:
    • Drug: Standard adjuvant systemic chemotherapy
    • Procedure: Hyperthermic intraperitoneal chemotherapy (HIPEC) with raltitrexed
  • 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)
    Interventions:
    • Drug: Standard adjuvant systemic chemotherapy
    • Procedure: Hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 11, 2016)
147
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02965248
Other Study ID Numbers  ICMJE 1608163-15
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guoxiang Cai, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Guoxiang Cai, M.D. Ph.D. Fudan University
PRS Account Fudan University
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP