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Combination Chemotherapy in Treating Patients With Stage III or Stage IV Melanoma

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ClinicalTrials.gov Identifier: NCT00003346
Recruitment Status : Completed
First Posted : April 25, 2003
Last Update Posted : June 25, 2013
Information provided by:

Study Description
Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy consisting of acetaminophen plus carmustine in treating patients who have stage III or stage IV melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Drug: acetaminophen Drug: acetylcysteine Drug: carmustine Phase 2

Detailed Description:


  • Determine the maximum tolerated dose (MTD) and the optimal biologic dose (OBD) of high-dose acetaminophen when given alone, and the MTD of carmustine when given with acetaminophen at the OBD in patients with metastatic melanoma (Phase I closed to accrual 3/7/2001).
  • Determine the dose of acetaminophen that results in maximal depletion of intracellular glutathione in these patients.
  • Assess the antitumor activity of high-dose acetaminophen in these patients.
  • Assess the toxicity and antitumor activity of carmustine when administered with high-dose acetaminophen in these patients.

OUTLINE: This is a dose-escalation study.

  • Phase I: (closed to accrual 3/7/2001) Patients receive a single oral dose of acetaminophen, then acetylcysteine IV over 20 hours, beginning 6-8 hours after the acetaminophen. This treatment is repeated 3 weeks later. On day 1 of the first treatment, patients also receive carmustine IV over 1 hour, before the acetylcysteine. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients each receive escalating doses of acetaminophen to determine the optimal biological dose (OBD). The OBD is defined as the lowest dose at or preceding the maximum tolerated dose (MTD) that results in maximal depletion of glutathione. The MTD is defined as the dose at which no more than 1 to 6 patients experience dose-limiting toxicity (DLT).

Once the OBD is established for acetaminophen, cohorts of 3-6 patients each receive escalating doses of carmustine. The MTD is defined as for acetaminophen. Dose escalation does not proceed until all patients are observed for 6 weeks after receiving carmustine.

Once the OBD for acetaminophen and MTD for carmustine are determined, 3 more patients are treated at 3 week intervals instead of 6 weeks. If no DLT is observed, this is the dose and schedule for the phase II portion of the study.

  • Phase II: A cohort of 14 patients receives oral acetaminophen and acetylcysteine IV every 3 weeks. Another cohort of 14 patients receives oral acetaminophen and acetylcysteine IV, then oral acetaminophen, carmustine IV, and acetylcysteine IV 3 weeks later. Patients continue therapy in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30-80 patients will be accrued for this study within 40 months.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Primary Purpose: Treatment
Official Title: Phase I-II Trial of High-Dose Acetaminophen With Carmustine in Patients With Metastatic Melanoma
Study Start Date : November 1997
Primary Completion Date : February 2003
Study Completion Date : February 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed stage IV melanoma or stage III melanoma not potentially curable by surgery
  • Phase I: (closed to accrual 3/7/2001) measurable or evaluable disease required
  • Phase II: At least 2 measurable subcutaneous or cutaneous metastases that are accessible for biopsy



  • Over 18

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified


  • WBC at least 4,000/mm^3
  • Hemoglobin at least 9 g/dL
  • Platelet count at least 100,000/mm^3
  • No active bleeding


  • AST less than 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 1.5 times ULN
  • PT/PTT within normal range


  • Not specified


  • No interstitial lung disease or unexplained interstitial infiltrates on chest x-ray
  • No chronic obstructive pulmonary disease
  • No asthma requiring treatment


  • No active infection requiring antimicrobial drugs
  • Not pregnant or nursing
  • Fertile patients must use effective barrier contraception
  • No allergies to acetaminophen or acetylcysteine


Biologic therapy:

  • At least 4 weeks since prior immunotherapy


  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin)
  • No prior nitrosoureas
  • No prior hepatic perfusions with chemotherapy

Endocrine therapy:

  • No concurrent oral contraceptives


  • At least 4 weeks since prior radiotherapy


  • Not specified


  • No concurrent vitamin, mineral, or garlic supplements
  • At least 7 days since prior garlic or alcohol
  • No concurrent treatment with medications known to affect P450 hepatic enzymes
  • No concurrent treatment with calcium channel blockers
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003346

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Study Chair: Paul B. Chapman, MD Memorial Sloan Kettering Cancer Center
More Information

ClinicalTrials.gov Identifier: NCT00003346     History of Changes
Other Study ID Numbers: 97-124
CDR0000066323 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: April 25, 2003    Key Record Dates
Last Update Posted: June 25, 2013
Last Verified: June 2013

Keywords provided by Memorial Sloan Kettering Cancer Center:
stage III melanoma
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents