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

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.

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.