A Random-Assignment Study of Hepatic Arterial Infusion of Melphalan with Venous Filtration via Peripheral Hepatic Perfusion (PHP) (Delcath System) Versus Best Alternative Care for Ocular and Cutaneous Melanoma Metastatic to the Liver
Investigator:
Richard Alexander, M.D.
Summary:
This is a randomized, open label study. A minimum of forty-six (46) eligible male and female patients with cutaneous or ocular melanoma with unresectable metastatic cancer to the liver will be enrolled into each of the 2 treatment arms in the study. Once screened and qualified, patients will be randomized either to the Delcath System treatment arm to receive the maximum tolerated dose of melphalan, 3 mg/kg, based upon ideal body weight or to the best alternative care including systemic dacarbazine, other systemic chemotherapy, intrahepatic therapy or supportive care medical management based on investigator's judgment. Patients who are randomized to best alternative care treatment arm are allowed to crossover to the Delcath System treatment if they failed the best alternative care therapy and showed progression of hepatic disease provided that they meet entry criteria as defined for the study.
Disease site:
Melanoma
Disease stage:
Metastatic
Condition:
Ocular and Cutaneous Melanoma
Intervention:
Delcath System to Deliver Melphalan
Phase:
III
Study number:
GCC0636
Eligibility*
(inclusion criteria)
1. Male or female patient greater than or equal to 18 years of age with a life expectancy of at least 3 months.
2. Patients must weigh greater than or equal to 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath System).
3. Histologically or cytologically proven cutaneous or ocular melanoma with metastases predominantly in the parenchyma of the liver. Disease must be measurable by CT and/or MRI. Evidence of limited unresectable extrahepatic disease on preoperative radiological studies is acceptable if the life-limiting component of progressive disease is in liver. Examples of limited extrahepatic disease that may be commonly encountered and considered acceptable include, but are not necessarily limited to: up to four pulmonary nodules each less than 1 cm in diameter, retroperitoneal lymph nodes less than 3 cm in diameter, skin or subcutaneous metastases that are fewer than 10 in number and less than 1 cm in diameter, asymptomatic bone metastases that have been or can be palliated with external beam radiation therapy, or a solitary metastasis to any site that can be resected.
4. Patient must have had no chemotherapy, radiotherapy, or biologic therapy for their malignancy in the month prior to treatment and must have recovered from all side effects of therapeutic and diagnostic interventions except those listed in Appendix I. For crossover patients from the BAC treatment arm with less than or equal to grade 1 treatment associated toxicity, the first PHP may be initiated 21 days after the last chemotherapy
5. Patient must have an ECOG performance standard of less than 3 at screening and on the day prior to treatment.
6. Patient must have adequate hepatic function as evidence by a total serum bilirubin less than 3.0 mg/dL and a PT within 2 seconds of the upper normal limit. AST/ALT must be less than or equal to 10 times upper limit of normal.
7. Patient must have a platelet count greater than 75,000/uL, Hgb greater than or equal to 9 mg/dL (correctable with transfusion), an ANC greater than or equal to 1.3 k/uL and a creatinine less than or equal to 1.5 mg/dL unless the measured creatinine clearance is greater than 60mL/min/1.73m2.
8. Confirmation of pathology by the Pathology Department of the investigational site.
9. Women who are premenopausal (have had a period within the past 12 months) must be willing to undergo hormonal suppression during treatment.
10. Patient must be aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks and voluntarily signed a written informed consent agreement, prior to any study procedure.
(exclusion criteria)
1. Patient with Childs B or C cirrhosis or with evidence of portal hypertension by history, endoscopy, or radiologic studies.
2. Patient with a history of congestive heart failure with an LVEF less than 40%.
3. Patient with significant COPD or other chronic pulmonary restrictive disease with PFT¿s indicating an FEV1 less than 30% or a DLCO less than 40% predicted for age.
4. Pregnant patient and nursing mother (because of the unknown effects of this therapy on the fetus or nursing infant).
5. Patient taking immunosuppressive drugs or requiring ongoing chronic anticoagulation.
6. Patient with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy
7. Patient with severe allergic reactions to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids (because a hepatic angiogram is needed for the Delcath System procedure).
8. Patient who is serologically positive for HIV, Hepatitis B surface antigen or Hepatitis C antibody is excluded from participating in the PK portion of the study but is eligible to enroll into the study and received treatment.
9. Patient with a known prior hypersensitivity reaction to melphalan.
10. Patients previously treated with regional hepatic therapy with melphalan.
11. Patients with resectable tumor(s) of the liver.
12. Patients with documented latex allergy.
13. Patients with a history of hypersensitivity to heparin in the presence of a heparin induced thrombocytopenia (HIT) anti-bodies
14. Patients with evidence of intracranial abnormalities which would put them at risk for bleeding with anticoagulation (e.g., stroke, active metastases).
Contact Person
Jagdish Shetty, MS 410-328-7680
* Note: This study may include eligibility criteria that are not listed here. For more information about the study or to find out if you are eligible, call 1-800-888-8823.
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