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Recurrent MelanomaPhase 3NCT00003789

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

A Phase 3 study testing isolated limb perfusion, melphalan and recombinant tumor necrosis factor family protein in people with Recurrent Melanoma and Stage III Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Melanoma, Stage III Melanoma
What is being tested?
isolated limb perfusion, melphalan and recombinant tumor necrosis factor family protein
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
216 participants
Where
1 siteUnited States
Study dates
Mar 1999to Jan 2004
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 53Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • American College of Surgeons Oncology Group

    Durham, North Carolina, 27705

Other trials in United States

About this study

Official title: 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.

Read the detailed description

OBJECTIVES:

  1. 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.

Being tested
isolated limb perfusion, melphalan, recombinant tumor necrosis factor family protein, pharmacological study, laboratory biomarker analysis
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • isolated limb perfusionDrug

    Also called isolated limb infusion

    Undergo isolated limb perfusion

  • melphalanDrug

    Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard

    Given via limb perfusion

  • recombinant tumor necrosis factor family proteinBiological

    Also called tumor necrosis factor, Tumor Necrosis Factor Family Protein

    Given via slow injection into the arterial line

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00003789
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: isolated limb perfusion; Drug: melphalan; Other: pharmacological study; Other: laboratory biomarker analysis
Arm IIExperimentalPatients 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.
Receives: Drug: isolated limb perfusion; Biological: recombinant tumor necrosis factor family protein; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 3 months after completion of study treatment

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

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

    Measured: Up to 1 month after completion of study treatment

Secondary outcomes (2)

  1. Local progression-free survival

    Time to event outcome models will be based on proportional hazard regression.

    Measured: Up to 12 years

  2. Overall survival

    Time to event models will be based on proportional hazard regression.

    Measured: Up to 12 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startMar 1999
  3. Primary completionJan 2004

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
216 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003789
Sponsor's protocol ID
NCI-2012-01843
Other IDs
Z0020, ACOSOG-Z0020, CDR0000066929, NCI-03-C-0137, U10CA076001
Status last verified
Jun 2013
First submitted
1 Nov 1999
Last updated
16 Jul 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing isolated limb perfusion, melphalan and recombinant tumor necrosis factor family protein in people with Recurrent Melanoma and Stage III Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 53 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CR proportion (time frame: Up to 3 months after completion of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003789.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2013; AzTrials last refreshed its copy on 2 Nov 2026.

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