A Phase II Study of Isolated Hepatic Perfusion (IHP) With Melphalan Followed by Temozolomide for Subjects With Unresectable Hepatic Metastases From Ocular Melanoma
- INCLUSION CRITERIA:
Histologically or cytologically proven measurable metastatic ocular melanoma confined to
the liver. Patients with limited sites of extra-hepatic disease and who have dominant
life-limiting disease in liver will be considered eligible if the extra-hepatic sites can
be treated with local ablative measures such as resection or external beam radiation
therapy. Patients with limited extra-hepatic disease will undergo IHP and treatment of
extra-hepatic disease in a sequence determined by the clinical presentation but all
patients will have had all disease treated prior to initiating temozolomide therapy.
Patients must have had no chemotherapy, radiotherapy, or biologic therapy for their
malignancy for 28 days prior to the liver perfusion and must have recovered from all side
effects except those outlined in appendix III.
Patients must have an ECOG performance standard of 0,1 or 2 prior to on-study and on the
day prior to treatment with IHP.
Patients must have adequate hepatic function as evidenced by bilirubin less than 2.0 mg/dL
and a PT equal to 2 seconds of the upper normal limit AST/ALT less than or equal to 10
Patients must be 18 years of age or greater and must be greater than 30 kg, because of
reason outlined in Section 6.2.
Patients must have a platelet count greater than 75,000, a HCT greater than 27.0, an ANC
greater than or equal to 1,500/ul, and a creatinine less than or equal to 1.5 mg/dL unless
the measured creatinine clearance is greater than 60 mL/min/1.73 m(2).
Patients must be aware of the neoplastic nature of his/her illness, the experimental
nature of the therapy , alternative treatments, potential benefits, and risks. The
patient must be willing to sign an informed consent.
Pregnant patients and nursing mothers will be excluded due to the unknown effects of
melphalan on the fetus or newborn.
Patients taking immunosuppressive drugs or on chronic anticoagulation will not be
Patients with active systemic infections are not eligible.
Patients with biopsy proven cirrhosis or evidence of significant portal hypertension by
history, endoscopy, or radiologic studies will be excluded.
Patients with a history of congestive heart failure with an LVEF less than 40% will be
Patients with COPD or other chronic pulmonary disease with PFT's less than 50% predicted
for age will be excluded.
Patients with a history or diagnosis of veno-occlusive disease (VOD) will be excluded.
Patients with chronic active hepatitis based on a positive serology test for surface
antigen B or C will be excluded if there is evidence of cirrhosis on pathology. If no
pathology specimen exists then evidence for cirrhosis will be determined based on
radiological studies and physical examination. If there are no indications of it then the
patient will be registered on study and a biopsy will be obtained at the time of
laparotomy for IHP with the expectation that occult clinically significant cirrhosis is
very unlikely. If cirrhosis is pathologically confirmed the patient will not undergo
treastment and be taken off study. Patients with radiographic or other signs of cirrhosis
will undergo percutaneous biopsy prior to registration.
Patients with a prior hypersensitivity reaction to melphalan, dacarbazine, or temozolomide
will be ineligible for study.