Clinical trial NCT01815359: 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
Official title: ICARuS (Intraperitoneal Chemotherapy After cytoReductive Surgery): A Multi-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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Appendix Cancer
Colorectal Cancer
Keywords: ICARuS
Intraperitoneal Chemotherapy
hyperthermic intraperitoneal chemotherapy
Optimal Surgical Debulking
Leucovorin
Floxuridine (FUDR)
Mitomycin
12-289
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: The Cleveland Clinic
name: Brigham and Women's Hospital
name: University of Miami
name: University of Pittsburgh Medical Center
name: Washington University School of Medicine
First posted: 2013-03-21
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: After the initial 212 patients are accrued, the final 70 patients will be accrued to only the appendiceal cohorts
Primary purpose: TREATMENT

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.


Eligibility 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 \> 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: surgical toxicity grade 3 to 5
timeFrame: up to 60 days
measure: chemotherapy toxicity grade 3 to 5
timeFrame: up to 60 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Consent and Follow up)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Consent and Follow up)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Consent and Follow up)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (Consent and Follow up)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Consent and Follow up)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Consent and Follow up)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Garrett Nash, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: