Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Locally Advanced Melanoma of the Arm or Leg

NCT00003789 | Completed Phase 3

• 6 other identifiers: NCI-2012-01843Z0020ACOSOG-Z0020CDR0000066929NCI-03-C-0137U10CA076001
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized phase III trial to compare the effectiveness of hyperthermic isolated limb perfusion of melphalan with or without tumor necrosis factor in treating patients who have locally advanced melanoma of the arm or leg. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Heating melphalan to several degrees above body temperature and infusing it only to the area around the tumor may kill more tumor cells. It is not yet known whether combining melphalan with tumor necrosis factor is more effective than melphalan alone in treating melanoma.

Conditions

Recurrent Melanoma; Stage III Melanoma

Outcome Measures

Primary Outcomes (2)

• CR proportion

  Response will be calculated based on the 3-month follow-up assessment of presence of absence of complete response. This will be done using the logistic regression model.

  Up to 3 months after completion of study treatment

• Incidence of adverse events, graded according to NCI CTC version 2.0

  The quantification and between-arm comparison of toxicity will be studied.

  Up to 1 month after completion of study treatment

Secondary Outcomes (2)

• Local progression-free survival

  Up to 12 years

• Overall survival

  Up to 12 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients undergo hyperthermic isolated perfusions of the lower limb by either the external iliac vessels or the common femoral vessels. Patients undergo perfusions of the upper extremity by the axillary artery and vein using an infraclavicular/axillary incision. Melphalan is introduced into the perfusion by slow injection over 5 minutes and allowed to remain for a total of 60 minutes.

Drug: isolated limb perfusion; Drug: melphalan; Other: pharmacological study; Other: laboratory biomarker analysis

Arm II

EXPERIMENTAL

Patients undergo hyperthermic isolated perfusions as in arm I. Tumor necrosis factor is administered by slow injection into the arterial line and allowed to remain for a total of 90 minutes. Melphalan is introduced into the perfusion as in arm I and allowed to remain for a total of 60 minutes.

Drug: isolated limb perfusion; Biological: recombinant tumor necrosis factor family protein; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

isolated limb perfusion DRUG

Undergo isolated limb perfusion

Also known as: isolated limb infusion

Arm I; Arm II

melphalan DRUG

Given via limb perfusion

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Arm I

recombinant tumor necrosis factor family protein BIOLOGICAL

Given via slow injection into the arterial line

Also known as: tumor necrosis factor, Tumor Necrosis Factor Family Protein

Arm II

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I; Arm II

laboratory biomarker analysis OTHER

Correlative studies

Arm I; Arm II

Eligibility Criteria

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

You may qualify if:

• Histologically proven locally advanced melanoma of an extremity
• One or more evaluable in-transit metastases
• All disease within the perfusion field of the extremity (with no local resection options short of amputation)
• Disease outside of perfusion field (with no local resection options short of amputation) if all the following are true:
• High tumor burden (more than 10 lesions or any single lesion greater than 3 cm)
• Presence of pain, edema, skin breakdown, or decreased mobility
• Greater than 80% of known tumor is within extremity perfusion field
• Life expectancy more than 6 months
• No brain metastases
• At least 1 bidimensionally measurable lesion
• Patients who received prior prophylactic isolated limb perfusion (ILP) must have 1 of the following:
• Disease-free interval for at least 6 months after prior ILP with melphalan
• Disease-free interval for at least 3 months after prior ILP with an agent other than melphalan
• Patients who received prior therapeutic ILP must have 1 of the following:
• Partial response of at least 3 months duration after prior ILP with melphalan

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

American College of Surgeons Oncology Group

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Melphalan; Tumor Necrosis Factors; Tumor Necrosis Factor-alpha

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Monokines; Blood Proteins

Study Officials

• Douglas Fraker

  American College of Surgeons

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: March 1, 1999
• Primary Completion: January 1, 2004
• Last Updated: July 16, 2013

Record last verified: 2013-06

Locations

US (1)