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

NCT01815359 | Active Not Recruiting Phase 2

• 1 other identifier: 12-289
• Study Type: interventional
• Target: 292
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Appendix Cancer; Colorectal Cancer

Keywords

ICARuS; Intraperitoneal Chemotherapy; hyperthermic intraperitoneal chemotherapy; Optimal Surgical Debulking; Leucovorin; Floxuridine (FUDR); Mitomycin; 12-289

Outcome Measures

Primary Outcomes (1)

• disease-free survival

  Documentation of tumor recurrence will be made based on surveillance CT/PET CT scans at time points as determined by attending radiologist, with clinical correlation from the treating physician.

  3 years

Secondary Outcomes (2)

• surgical toxicity grade 3 to 5

  up to 60 days

• chemotherapy toxicity grade 3 to 5

  up to 60 days

Study Arms (4)

Appendiceal, no chemotherapy within 6 months prior to surgery

EXPERIMENTAL

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 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; Drug: HIPEC with Mitomycin-C; Drug: EPIC with FUDR and Leucovorin

Appendiceal, chemotherapy within 6 months prior to surgery

EXPERIMENTAL

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 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; Drug: HIPEC with Mitomycin-C; Drug: EPIC with FUDR and Leucovorin

Colorectal, no chemotherapy within 6 months prior to surgery

EXPERIMENTAL

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 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; Drug: HIPEC with Mitomycin-C; Drug: EPIC with FUDR and Leucovorin

Colorectal, chemotherapy within 6 months prior to surgery

EXPERIMENTAL

First, patients will be stratified by previous systemic chemotherapy and by the organ of origin as determined by the PI or Co-PI. 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; Drug: HIPEC with Mitomycin-C; Drug: EPIC with FUDR and Leucovorin

Interventions

Cytoreductive Surgery PROCEDURE

Optimal Surgical Debulking

Appendiceal, chemotherapy within 6 months prior to surgery; Appendiceal, no chemotherapy within 6 months prior to surgery; Colorectal, chemotherapy within 6 months prior to surgery; Colorectal, no chemotherapy within 6 months prior to surgery

HIPEC with Mitomycin-C DRUG

Appendiceal, chemotherapy within 6 months prior to surgery; Appendiceal, no chemotherapy within 6 months prior to surgery; Colorectal, chemotherapy within 6 months prior to surgery; Colorectal, no chemotherapy within 6 months prior to surgery

EPIC with FUDR and Leucovorin DRUG

Appendiceal, chemotherapy within 6 months prior to surgery; Appendiceal, no chemotherapy within 6 months prior to surgery; Colorectal, chemotherapy within 6 months prior to surgery; Colorectal, no chemotherapy within 6 months prior to surgery

Eligibility Criteria

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

You may qualify if:

• 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 \> 75,000/ 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.

You may not qualify if:

• Subjects who have previously undergone intraperitoneal chemotherapy.
• Subjects with classical carcinoid
• Tumors of low malignant potential
• 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.
• 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 60 days of enrollment and/or were cleared by MSK cardiology.
• 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.

Sponsors & Collaborators

• The Cleveland Clinic: collaborator
• Brigham and Women's Hospital: collaborator
• University of Miami: collaborator
• University of Pittsburgh Medical Center: collaborator
• Washington University School of Medicine: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (9)

University of Miami

Miami, Florida, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Basking Ridge (Consent and Follow up)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Consent and Follow up)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Consent and Follow up)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Consent and Follow up)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Consent and Follow up)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Consent and Follow up)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Appendiceal Neoplasms; Colorectal Neoplasms

Interventions

Cytoreduction Surgical Procedures; Hyperthermic Intraperitoneal Chemotherapy; Mitomycin; Floxuridine; Leucovorin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes

Study Officials

• Garrett Nash, MD, MPH

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After the initial 212 patients are accrued, the final 70 patients will be accrued to only the appendiceal cohorts

Study Record Dates

• First Submitted: March 13, 2013
• First Posted: March 21, 2013
• Study Start: March 1, 2013
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (9)