Mitomycin C or Floxuridine and Leucovorin Calcium during or after Surgery in Treating Patients with Appendiceal, Colon, or Rectal Cancer

This randomized phase II trial studies how well mitomycin C or floxuridine and leucovorin calcium during or after surgery works in treating patients with appendiceal, colon, or rectal cancer. Drugs used in chemotherapy, such as mitomycin C, floxuridine, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether heating a chemotherapy solution and infusing it directly into the abdomen during surgery kills more tumor cells than infusing a chemotherapy solution directly into the abdomen after surgery.

Inclusion Criteria

• Clinical diagnosis of appendiceal or colorectal neoplasm with peritoneal mucinosis or metastasis
• Patient must be planning to undergo complete cytoreduction of all peritoneal disease
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelets > 75,000/uL
• Creatinine < 1.5 x the upper limit of normal (ULN) or calculated creatinine clearance of >= 50 ml/min
• Bilirubin less than 1.5 mg/dL; (except in patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/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 Memorial Sloan Kettering (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 (leucovorin calcium), or mitomycin (mitomycin C) 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 OBJECTIVES:

I. To compare the 3-year disease-free survival of each treatment arm.

SECONDARY OBJECTIVES:

I. To compare the toxicity of each treatment.

TERTIARY OBJECTIVES:

I. To measure quality of life and nutrition parameters in subjects undergoing each treatment.

II. To conduct exploratory correlative studies of biomarkers.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

HIPEC ARM: Patients receive hyperthermic mitomycin C intraperitoneally (IP) over 100 minutes during surgery.

EPIC ARM: Patients receive floxuridine IP over 60-120 minutes and leucovorin calcium intravenously (IV) over 2 hours on days 1-3 after surgery.

After completion of study treatment, patients are followed up at 6 and 12 weeks and then at 6, 9, 12, 15, 18, 24, 30, and 36 months.

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Garrett Nash