Temozolomide and Radiation Therapy in Treating Patients With Stage IV Malignant Melanoma With Measurable and Unresectable Cancer of the Central Nervous System

A Systemic Temozolomide Treatment Of Melanoma Present In The Central Nervous System

RATIONALE: Drugs used in chemotherapy, such as temozolomide, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining temozolomide with radiation therapy may make the tumor cells more sensitive to radiation therapy and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating patients with stage IV malignant melanoma with measurable and unresectable cancer limited to the central nervous system.

Study Overview

• Status: Terminated
• Conditions: Metastatic Cancer; Melanoma (Skin)
• Intervention / Treatment: Radiation: radiation therapy; Drug: temozolomide

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with stage IV malignant melanoma with measurable and unresectable disease of the central nervous system treated with temozolomide and radiotherapy.

Secondary

• Determine the safety of this regimen in these patients.
• Determine the survival of patients treated with this regimen.
• Determine the effect of this regimen on performance status and mental status of these patients.
• Determine the response of extra-cranial disease in patients treated with this regimen.

OUTLINE: Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 18-41 patients will be accrued for this study within 13-30 months.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • Des Moines, Iowa, United States, 50316-2301
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
    • West Des Moines, Iowa, United States, 50266
      • Medical Oncology and Hematology Associates - West Des Moines
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Lichfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA at Maplewood Cancer Center
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Cancer Center
    • St Paul, Minnesota, United States, 55102
      • St. Joseph's Hospital
    • St. Louis Park, Minnesota, United States, 55416
      • Park Nicollet Health Services
    • St. Paul, Minnesota, United States, 55102
      • United Hospital
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
  • Ohio
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sioux Valley Hospital and University of South Dakota Medical Center
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC

Participation Criteria

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 malignant melanoma with measurable and unresectable disease limited to the central nervous system (CNS)

  • Study entry within 14 days of diagnosis of brain metastases
• Recursive partitioning analysis class I or II
• Disease for which no known standard therapy exists that is potentially curative or proven capable of extending life expectancy
• No meningeal carcinomatosis based on imaging studies or on positive results from CSF analysis
• No evidence of metastatic disease outside of the CNS

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• AST no greater than 3 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent uncontrolled infection
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer treated with local resection only
• No prior allergy or intolerance to dacarbazine
• No hypersensitivity to temozolomide or any of its components

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy

Chemotherapy

• No prior temozolomide
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

Endocrine therapy

• Concurrent steroids allowed if dose stable for at least 7 days prior to CNS imaging

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 15% of the bone marrow
• No prior radiotherapy to the head and neck area
• No prior radiosurgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: radiation + temozolomide; Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months.	Radiation: radiation therapy; Drug: temozolomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Confirmed response rate	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Up to 5 years
Overall survival	Up to 5 years
Change in performance status	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Schild SE, Behl D, Markovic SN, Brown PD, Sande JR, Deming RL, Rowland KM Jr, Bearden JD. Brain metastases from melanoma: is there a role for concurrent temozolomide in addition to whole brain radiation therapy? Am J Clin Oncol. 2010 Dec;33(6):633-6. doi: 10.1097/COC.0b013e3181c4c54b.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): March 1, 2005
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: September 10, 2003
• First Submitted That Met QC Criteria: September 10, 2003
• First Posted (Estimate): September 11, 2003

Study Record Updates

• Last Update Posted (Estimate): December 15, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; tumors metastatic to brain
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: N0274; CDR0000327811 (Registry Identifier: PDQ (Physician Data Query)); NCI-2012-02554 (Registry Identifier: CTRP (Clinical Trials Reporting System))