ICARuS Post-operative Intraperitoneal Chemotherapy (EPIC) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) After Optimal Cytoreductive Surgery (CRS) for Neoplasms of the Appendix, Colon or Rectum With Isolated Peritoneal Metastasis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01815359
First received: March 13, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

This is the first randomized trial comparing Early post-operative intraperitoneal chemotherapy (EPIC) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancer. The purpose of this study is to find out what effects, good and/or bad, EPIC and HIPEC after cytoreductive surgery have on the patient and the appendiceal, rectal or colon cancer.


Condition Intervention Phase
Appendix Cancer
Colorectal Cancer
Procedure: Cytoreductive Surgery
Drug: HIPEC with Mitomycin-C
Drug: EPIC with FUDR and Leucovorin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ICARuS (Intraperitoneal Chemotherapy After cytoReductive Surgery): A Single-center, Randomized Phase II Trial of Early Post-operative Intraperitoneal Chemotherapy (EPIC) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) After Optimal Cytoreductive Surgery (CRS) for Neoplasms of the Appendix, Colon or Rectum With Isolated Peritoneal Metastasis

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • disease-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Documentation of tumor recurrence will be made based on surveillance CT scans at time points as determined by attending radiologist, with clinical correlation from the treating physician.


Secondary Outcome Measures:
  • surgical toxicity grade 3 to 5 [ Time Frame: up to 60 days ] [ Designated as safety issue: Yes ]
    We will evaluate toxicity up to 60 days postoperatively for any surgical Grade 3-5 complications or chemotherapy related Grade 4 or 5 toxicities. Surgical morbidity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  • chemotherapy toxicity grade 4 or 5 [ Time Frame: up to 60 days ] [ Designated as safety issue: Yes ]
    We will evaluate toxicity up to 60 days postoperatively for any surgical Grade 3-5 toxicity or chemotherapy related Grade 4 or 5 toxicities.


Estimated Enrollment: 220
Study Start Date: March 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Appendiceal, no chemotherapy within 6 months prior to surgery

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the Colorectal Disease Management Team.

  1. Exposure to chemotherapy in the prior 6 months vs. no such exposure
  2. Appendix vs. Colon or Rectum Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.
Procedure: Cytoreductive Surgery
Optimal Surgical Debulking
Drug: HIPEC with Mitomycin-C Drug: EPIC with FUDR and Leucovorin
Experimental: Appendiceal, chemotherapy within 6 months prior to surgery

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the Colorectal Disease Management Team.

  1. Exposure to chemotherapy in the prior 6 months vs. no such exposure
  2. Appendix vs. Colon or Rectum • Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.
Procedure: Cytoreductive Surgery
Optimal Surgical Debulking
Drug: HIPEC with Mitomycin-C Drug: EPIC with FUDR and Leucovorin
Experimental: Colorectal, no chemotherapy within 6 months prior to surgery

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the Colorectal Disease Management Team.

  1. Exposure to chemotherapy in the prior 6 months vs. no such exposure
  2. Appendix vs. Colon or Rectum • Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.
Procedure: Cytoreductive Surgery
Optimal Surgical Debulking
Drug: HIPEC with Mitomycin-C Drug: EPIC with FUDR and Leucovorin
Experimental: Colorectal, chemotherapy within 6 months prior to surgery

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the Colorectal Disease Management Team.

  1. Exposure to chemotherapy in the prior 6 months vs. no such exposure
  2. Appendix vs. Colon or Rectum • Then, patients will be randomly assigned in the operating room, by envelope, to either HIPEC (Group A) or EPIC (Group B) after the operating surgeon determines that the patient is optimally cytoreduced to nodules no greater than 2.5mm.
Procedure: Cytoreductive Surgery
Optimal Surgical Debulking
Drug: HIPEC with Mitomycin-C Drug: EPIC with FUDR and Leucovorin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient's age 18 years or older, both genders.
  • Clinical diagnosis of appendiceal or colorectal neoplasm with peritoneal mucinosis or metastasis.
  • Patient must be planning to undergo complete cytoreduction of all peritoneal disease.
  • ECOG performance status ≤ 1.
  • Hematology: ANC ≥ 1,500/ μL; Platelets > 100,000/ μL.
  • Adequate Renal function Creatinine <1.5 x the upper limit of normal (ULN) or calculated creatinine clearance of ≥ 50ml/min.
  • Adequate Hepatic function: Bilirubin less than 1.5mg/dL; (except in patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0mg/dL).
  • Women with childbearing potential who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive method. Reliable contraception should be used from trial screening and must be continued throughout the study. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant.
  • A man participating in this study must agree to utilize reliable barrier form of contraception for the duration of the study.
  • Signed and dated written informed consent to participate in this clinical trial must be obtained prior to any study procedure.
  • Subjects with a history of endometrial cancer are eligible only if they presented with a stage lower than 1A and if the histology was a subtype other than poorly differentiated.

Exclusion Criteria:

  • Subjects who have previously undergone complete cytoreduction and/or intraperitoneal chemotherapy.
  • Subjects with classical carcinoid
  • Tumors of low malignant potential
  • Subjects who have received prior radiation to any portion of the abdominal cavity or pelvis are excluded.

Other prior malignancies, except for cured non-melanoma skin cancer, curatively treated in situ carcinoma of the cervix, adequately treated malignancies for which there has been no evidence of activity for more than 3 years or indolent tumors for which observation over three years is a reasonable option.

  • Presence of clinically apparent or suspected metastasis to sites other than lymph nodes or peritoneal surfaces.
  • Women who are pregnant or lactating.
  • Subjects with a condition which may interfere with the subjects' ability to understand the requirements of the study.
  • Known HIV
  • Active coronary artery disease (defined as unstable angina or a positive cardiac stress test).
  • Subjects with a history of coronary artery disease may be included if they have had a normal stress test within 30 days of enrollment.

Uncontrolled hypertension defined as >140/90 and not cleared for surgery at the time of consent.

  • New York Heart Association (NYHA) Class II or higher Congestive heart failure.
  • Restrictive or obstructive pulmonary disease that would limit study compliance or place the patient at unacceptable risk for participation in the study.
  • History of cerebrovascular disease. that would limit study compliance or place the patient at unacceptable risk for participation in the study.

Subjects with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study, or places them at an unacceptable risk for participation in the study.

  • Patients with known floxuridine, leucovorin ,or mitomycin allergy.
  • Evidence of extensive intraperitoneal adhesions at the time of surgery which prohibits intraperitoneal therapy, as determined by the operating surgeon.
  • Any condition that would preclude the ability to deliver appropriate IP therapy.
  • Use of an oral medication, lacking a suitable non-oral substitute, that if held for up to ten days, would be felt an unacceptable risk by the investigator.
  • Life expectancy < 12 weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01815359

Contacts
Contact: Garrett Nash, MD, MPH 646-888-3086
Contact: Andrea Cercek, MD 646-888-4189

Locations
United States, New Jersey
Memorial Sloan Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Garrett Nash, MD    646-888-3086      
United States, New York
Memorial Sloan Kettering Cancer Center Commack Recruiting
Commack, New York, United States, 11725
Contact: Garrett Nash, MD    646-888-3086      
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Garrett Nash, MD, MPH    646-888-3086      
Contact: Andrea Cercek, MD    646-888-4189      
Principal Investigator: Garrett Nash, MD, MPH         
Memorial Sloan Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Garrett Nash, MD    646-888-3086      
Memorial Sloan Kettering Cancer Center Sleepy Hollow Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Garrett Nash, MD    646-888-3086      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Garrett Nash, MD, MPH Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01815359     History of Changes
Other Study ID Numbers: 12-289
Study First Received: March 13, 2013
Last Updated: August 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
ICARuS
Intraperitoneal Chemotherapy
hyperthermic intraperitoneal chemotherapy
Optimal Surgical Debulking
Leucovorin
Floxuridine (FUDR)
Mitomycin
12-289

Additional relevant MeSH terms:
Appendiceal Neoplasms
Colorectal Neoplasms
Fever
Neoplasm Metastasis
Cecal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Cecal Diseases
Intestinal Diseases
Colonic Diseases
Rectal Diseases
Body Temperature Changes
Signs and Symptoms
Neoplastic Processes
Pathologic Processes
Mitomycins
Mitomycin
Leucovorin
Levoleucovorin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014