Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma

NCT00324727 | Completed Phase 3

• 3 other identifiers: CDR0000468944NCI-06-C-0088NCI-P6701
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 12

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving melphalan directly into the arteries around the tumor may kill more tumor cells. It is not yet known whether hepatic arterial infusion with melphalan is more effective than standard therapy in treating liver metastases due to melanoma. PURPOSE: This randomized phase III trial is studying hepatic arterial infusion with melphalan to see how well it works compared to standard therapy in treating patients with unresectable liver metastases due to melanoma.

Conditions

Intraocular Melanoma; Melanoma (Skin); Metastatic Cancer

Keywords

liver metastases; extraocular extension melanoma; stage IV melanoma; recurrent melanoma; recurrent intraocular melanoma; metastatic intraocular melanoma; iris melanoma; ciliary body and choroid melanoma, medium/large size

Outcome Measures

Primary Outcomes (1)

• Hepatic progression free survival

  Treatment to time of progression

Study Arms (2)

Arm I

EXPERIMENTAL

Patients undergo an isolated hepatic arterial infusion of melphalan over 30 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response undergo 2 additional courses in the absence of ongoing or increasing toxicity.

Drug: melphalan

Arm II

ACTIVE COMPARATOR

Patients receive the best alternative therapy comprising supportive care, systemic or regional chemotherapy, hepatic artery (chemo)-embolization, or any other appropriate therapy at the National Cancer Institute or therapy at the discretion of their physician. Patients may cross over to arm I if they have evidence of disease progression.

Drug: regional chemotherapy; Drug: systemic chemotherapy; Procedure: hepatic artery embolization

Interventions

melphalan DRUG

Given throug isolated hepatic artery infusion

Arm I

regional chemotherapy DRUG

Patients receive the best alternative therapy

Arm II

systemic chemotherapy DRUG

Patients receive the best alternative therapy

Arm II

hepatic artery embolization PROCEDURE

Patients receive the best alternative therapy

Arm II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed liver metastases secondary to cutaneous or ocular melanoma * Unresectable disease * Predominantly in the parenchyma of the liver * Measurable disease by CT scan and/or MRI * Limited unresectable extrahepatic disease allowed provided the life-limiting component of progressive disease is in the liver, including, but not limited to, any of the following: * Up to 4 pulmonary nodules, each \< 1 cm in diameter * Retroperitoneal lymph nodes \< 3 cm in diameter * Less than 10 skin or subcutaneous metastases \< 1 cm in diameter * Asymptomatic bone metastases that are eligible for or have undergone palliative external-beam radiotherapy * Solitary metastasis to any site that can be resected PATIENT CHARACTERISTICS: * Life expectancy ≥ 3 months * ECOG performance status 0-2 * Bilirubin \< 3.0 mg/dL * PT within 2 seconds of upper limit of normal (ULN) * AST/ALT ≤ 10 times ULN * Platelet count \> 75,000/mm\^3 * Hematocrit \> 27% (may be achieved with a transfusion) * Absolute neutrophil count ≥ 1,300/mm\^3 * Creatinine ≤ 1.5 mg/dL OR creatinine clearance \> 60 mL/min * Fertile patients must use effective contraception * Not pregnant or nursing * Negative pregnancy test * No history of congestive heart failure * LVEF ≥ 40% * No significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease * FEV\_1 ≥ 30% * DLCO ≥ 40% of predicted * Weight ≥ 35 kg * No untreated active bacterial infection with systemic manifestations (e.g., malaise, fever, and leucocytosis) * No severe allergic reactions to iodine contrast unless reaction can be controlled by antihistamines and/or steroids * No known hypersensitivity to melphalan * No positive serology for HIV, hepatitis B surface antigen, or hepatitis C antibody (pharmacokinetics portion of the study only) * No known latex allergy * No Childs B or C cirrhosis * No evidence of portal hypertension by history, endoscopy, or radiological study * No prior history of gastrinoma PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 1 month since prior chemotherapy, radiotherapy, or biologic therapy for this cancer and recovered * No prior regionally delivered melphalan * No prior Whipple procedure * No concurrent immunosuppressive therapy * No concurrent chronic anticoagulation therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Delcath Systems Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

John Wayne Cancer Institute at Saint John's Health Center

Santa Monica, California, 90404, United States

Location

Swedish Medical Center

Englewood, Colorado, 80113, United States

Location

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

Carol G. Simon Cancer Center at Morristown Memorial Hospital

Morristown, New Jersey, 07962-1956, United States

Location

Cancer Center of Albany Medical Center

Albany, New York, 12208, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210-1240, United States

Location

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, 97213-2967, United States

Location

St. Luke's Cancer Network at St. Luke's Hospital

Bethlehem, Pennsylvania, 18015, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0361, United States

Location

Related Links

• Publication of Results

MeSH Terms

Conditions

Uveal Melanoma; Melanoma; Neoplasm Metastasis

Interventions

Melphalan; Chemotherapy, Cancer, Regional Perfusion; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Combined Modality Therapy

Study Officials

• Marybeth S. Hughes, MD

  NCI - Surgery Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2006
• First Posted: May 11, 2006
• Study Start: February 1, 2006
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: June 21, 2021

Record last verified: 2021-06

Locations

US (12)