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

June 24, 2013 updated by: Memorial Sloan Kettering Cancer Center

Phase I-II Trial of High-Dose Acetaminophen With Carmustine in Patients With Metastatic Melanoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • 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 Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Phase 2

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
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • Over 18

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

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

Hepatic:

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

Renal:

  • Not specified

Pulmonary:

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

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior immunotherapy

Chemotherapy:

  • 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

Radiotherapy:

  • At least 4 weeks since prior radiotherapy

Surgery:

  • Not specified

Other:

  • 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

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

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Paul B. Chapman, MD, Memorial Sloan Kettering Cancer Center

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

November 1, 1997

Primary Completion (Actual)

February 1, 2003

Study Completion (Actual)

February 1, 2003

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

April 24, 2003

First Posted (Estimate)

April 25, 2003

Study Record Updates

Last Update Posted (Estimate)

June 25, 2013

Last Update Submitted That Met QC Criteria

June 24, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 97-124
  • CDR0000066323 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-H98-0014

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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