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

July 15, 2013 updated by: National Cancer Institute (NCI)

A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion and Melphalan With and Without Tumor Necrosis Factor in Patients With Localized Advanced Extremity Melanoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OBJECTIVES:

I. Compare hyperthermic isolated limb perfusion with melphalan with or without tumor necrosis factor, in terms of response proportion for lesions in the perfusion field, in patients with locally advanced extremity melanoma.

II. Compare the local recurrence-free survival, improvement in regional symptoms related to tumor, and overall survival in patients treated with these regimens.

III. Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor burden (high vs low), prior reperfusion (melphalan vs other), regional nodal site (yes vs no), and participating center. Patients are randomized to one of two treatment arms.

ARM I: 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.

ARM II: 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.

Patients are followed within 6 weeks, at 3, 6, and 12 months, every 6 months for 4 years, and then annually thereafter.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
216

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • American College of Surgeons Oncology Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
    • Stable response or disease progression after ILP without melphalan (performed at least 3 months prior to study)
  • Performance status - ECOG 0-2
  • Performance status - Zubrod 0-2
  • See Disease Characteristics
  • Platelet count at least 100,000/mm^3
  • WBC greater than 2,500/mm^3
  • Hemoglobin greater than 9 g/dL
  • Bilirubin less than 1.25 times ULN
  • AST and ALT less than 2 times ULN
  • Alkaline phosphatase less than 2 times ULN
  • Coagulation studies normal or within 1 second of upper limit of normal (ULN)
  • Creatinine less than 1.5 mg/dL
  • Creatinine clearance greater than 50 mL/min
  • Calcium less than 12 mg/dL
  • No severe peripheral vascular disease (claudication or other ischemic peripheral vascular disease [e.g., venous thrombosis or occlusive peripheral arterial disease])
  • No New York Heart Association class II-IV heart disease (congestive heart failure)
  • No uncontrolled or life-threatening cardiac arrhythmia
  • No myocardial infarction within the past year
  • No unstable angina
  • No symptomatic cerebral or carotid artery disease
  • No pulmonary embolism within the past year
  • Other prior malignancy allowed if completed curative therapy, disease-free for at least 5 years, and at low risk for recurrence
  • No active peptic ulcer disease within the past year
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known melphalan hypersensitivity
  • No known hypersensitivity to any component of tumor necrosis factor alpha formulation
  • No contraindications to ionotropic agents (e.g., dopamine or neosynephrine)
  • No concurrent infections uncontrolled with antibiotics
  • HIV negative
  • At least 1 month since prior biologic therapy
  • See Disease Characteristics
  • At least 1 month since prior chemotherapy
  • At least 4 months since prior isolated limb perfusion
  • At least 1 month since prior radiotherapy
  • See Disease Characteristics
  • At least 12 months since prior coronary artery surgery or angioplasty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm I
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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: isolated limb perfusion
Undergo isolated limb perfusion
Other Names:
  • isolated limb infusion
Drug: melphalan
Given via limb perfusion
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Experimental: Arm II
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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: isolated limb perfusion
Undergo isolated limb perfusion
Other Names:
  • isolated limb infusion
Biological: recombinant tumor necrosis factor family protein
Given via slow injection into the arterial line
Other Names:
  • tumor necrosis factor
  • Tumor Necrosis Factor Family Protein

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
CR proportion
Time Frame: Up to 3 months after completion of study treatment
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
Time Frame: Up to 1 month after completion of study treatment
The quantification and between-arm comparison of toxicity will be studied.
Up to 1 month after completion of study treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Local progression-free survival
Time Frame: Up to 12 years
Time to event outcome models will be based on proportional hazard regression.
Up to 12 years
Overall survival
Time Frame: Up to 12 years
Time to event models will be based on proportional hazard regression.
Up to 12 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Douglas Fraker, American College of Surgeons

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 1999

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2004

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 1, 1999

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2003

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 16, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 15, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCI-2012-01843
  • U10CA076001 (U.S. NIH Grant/Contract)
  • Z0020
  • ACOSOG-Z0020
  • CDR0000066929
  • NCI-03-C-0137

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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