Protocol Number: 06-C-0088

Title:

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

Number:

06-C-0088

Summary:

Background:

-The chemotherapy drug melphalan has been used with some success in treating cancer in the liver.

-Melphalan is less toxic if given directly into the blood vessels in the liver instead of through an IV line, and can therefore be given in higher, more effective doses. However, the drug can be given only once this way, because this method requires major surgery.

-A different method of giving chemotherapy directly to the liver without a major operation is called peripheral hepatic perfusion (PHP). Special catheters (plastic tubes) called the DelCath system are positioned in the blood vessels going into and out of the liver through small puncture holes in the skin and the melphalan is given through these catheters.

Objectives:

-To determine if chemotherapy delivered through the DelCath system is effective in treating and shrinking liver tumors.

-To determine the number and severity of side effects associated with the DelCath liver perfusion system.

Eligibility:

-Patients 18 years old or older with eye or skin melanoma that has spread to the liver.

-Patients' liver tumors cannot be removed surgically.

-Patients whose tumor has spread to limited sites beyond the liver if the tumors outside the liver cannot be treated with surgery and if the life-limiting disease is progressive cancer in the liver.

Design:

-Participants are randomly assigned to receive standard treatment or liver perfusion with the DelCath system. Liver perfusion is done under general anesthesia.

-Patients receiving liver perfusion are admitted to the hospital for 3 to 5 days for the procedure as follows:

---Catheters are placed into the artery that supplies blood to the liver, the vein that drains the liver, and a large vein under the collarbone or in the neck to create a separate circulation for the liver, similar to the heart-lung bypass in open-heart surgery.

---With the catheters in place, melphalan is perfused into the liver for 30 minutes. The circulation to the liver remains separate and the blood is filtered through the DelCath system for another 30 minutes after melphalan is given to remove as much of it as possible from the blood coming out of the liver.

---Patients are observed in the intensive care unit for 24 hours after the procedure.

---Patients may receive liver perfusion treatments about every 4 weeks for up to 6 treatments.

-Patients receiving standard treatment may be treated by their referring physician or at the Clinical Center.

-Patients in both treatment groups have blood tests and imaging tests at 6 weeks and 12 weeks to evaluate treatment response. These tests are repeated every 2 months the first year, every 3 months the second year, every 4 months the third year, every 6 months the fourth year and yearly thereafter.

-Patients receiving liver perfusion whose tumor grows or spreads outside the liver are taken off the study. Patients receiving standard treatment whose tumor grows are offered liver perfusion treatment.

-Patients in both groups who go off study continue to be contacted by phone every 6 months for the first 2 years and then each year thereafter.

-The study will include 46 patients.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Male or female patients greater than or equal to 18 years of age with a life expectancy of at least 3 months.

Histologically or cytologically proven cancer, predominantly in the parenchyma of the liver with one of the following histologies: cutaneous or ocular melanoma. 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. Patients previously treated with regionally delivered melphalan will not be considered for this trial.

Scans used to determine eligibility must be performed within 14 days prior to randomization. An MRI of the liver is required at screening to validate that CT accurately reflects the extent of disease in the liver.

Patients 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.

Patients must have an ECOG performance standard of lees than 3 at on study and on the day prior to treatment.

Patients 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.

Patients must have a platelet count greater than 75,000/microliter, an Hgb greater than or equal to 9gm/d/l (correctable with transfusion), an ANC greater than or equal to 1.3 k/microliter and a creatinine less than or equal to 1.5 mg/dL unless the measured creatinine clearance is greater than 60 microliter/min/1.73m(2).

Women who are premenopausal (have had a period within the past 12 months) must be willing to undergo hormonal suppression during treatment.

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 prior to any study procedure.

EXCLUSION CRITERIA:

Patients with a history of bleeding disorders (e.g., nose bleeds, bleeding ulcers) or evidence of intracranial abnormalities which would put them at risk for bleeding with anticoagulation (e.g., stroke, active metastases) will be excluded.

Patients with Childs B or C cirrhosis or with evidence of 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 excluded.

Patients 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 will be excluded.

Patients weighing less than 35 kg will be excluded as it is likely that their femoral artery and vein will not accommodate the percutaneous catheters.

Pregnant patients and nursing mothers will be excluded because of the unknown effects of this therapy on the fetus or nursing infants.

Patients taking immunosuppressive drugs or requiring ongoing chronic anticoagulation will not be eligible.

Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy.

Patients with severe allergic reactions to iodine contrast which cannot be controlled by premedication with antihistamines and steroids are not eligible as a hepatic angiogram is needed for this procedure.

Patients with a known prior hypersensitivity reaction to melphalan will be excluded.

Patients with resectable tumor(s) of the liver will be excluded.

Patients who are serologically positive for HIV, Hepatitis B surface antigen or Hepatitis C antibody are excluded from participating in the PK portion of the study but are eligible to enroll into the study and receive treatment.

Patients with a documented latex allergy.

Patients with a history of hypersensitivity to heparin in the presence of a heparin induced thrombocytopenia (HIT) anti-bodies.

Patients with a history of gastrinoma or who have undergone a Whipple procedure.

Special Instructions:

Currently Not Provided

Keywords:

Regional Chemotherapy

Response Rate

Duration of Response

Disease Free and Overall Survival

Patterns of Recurrence

Recruitment Keyword(s):

Melanoma

Ocular Melanoma

Cutaneous Melanoma

Condition(s):

Ocular and Cutaneous Melanoma

Investigational Drug(s):

Melphalan

Investigational Device(s):

DelCath Systems

Intervention(s):

Drug: Melphalan

Device: DelCath Systems

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin. 2003 Jan-Feb;53(1):5-26.

Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998 Oct 15;83(8):1664-78.

Shields CL. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Trans Am Ophthalmol Soc. 2000;98:471-92.

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