RATIONALE: Penicillamine may stop the growth of glioblastomas by stopping blood flow to the tumor. A diet low in copper may interfere with the growth of brain tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining these therapies may be effective in treating glioblastoma.

PURPOSE: Phase II trial to study the effectiveness of penicillamine, a low copper diet, and radiation therapy in treating patients who have newly diagnosed glioblastoma.

Condition	Treatment or Intervention	Phase
adult glioblastoma multiforme	Drug: penicillamine  Drug: pyridoxine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the effect of penicillamine on survival and time to progression in adults with newly diagnosed glioblastoma.

II. Determine the effect of penicillamine on the reduction of serum copper in these patients.

III. Determine whether penicillamine reduces the tumor volume, vascularity, invasion, and edema in these patients.

PROTOCOL OUTLINE: Patients receive oral penicillamine on the following schedule: Week 1: once daily Week 2: two times daily Week 3: three times daily Week 4: four times daily Week 5 to end of study: increased dose four times daily.

Patients also receive oral pyridoxine daily and maintain a low copper diet (no greater than 0.5 mg/day). This regimen is continued for up to 2 years in the absence of disease progression or unacceptable toxicity. Radiotherapy is administered over 6 weeks, beginning on day 1 of penicillamine therapy.

Patients are followed every 2 months until death.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven supratentorial grade IV astrocytoma (glioblastoma multiforme)

--Prior/Concurrent Therapy--

• Biologic therapy: No prior immunotherapy for brain tumor; No prior biologic therapy for brain tumor, including: Immunotoxins; Immunoconjugates; Antisense; Peptide receptor antagonists; Interferons; Interleukins; Tumor infiltrating lymphocytes; Lymphokine activated killer cells; Gene therapy; No concurrent growth factors (e.g., filgrastim or epoetin alfa)
• Chemotherapy: No prior chemotherapy for brain tumor
• Endocrine therapy: Must be on stable corticosteroid regimen for at least 1 week (at least 5 days); No other prior hormonal therapy for brain tumor
• Radiotherapy: No prior radiotherapy for brain tumor
• Surgery: Recovered from prior surgery
• Other: No concurrent investigational agents; No concurrent gold compounds (auronofin, gold sodium thiomalate); No concurrent herbal dietary supplements

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3000/mm3; Absolute neutrophil count at least 1500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 10.0 g/dL; No serious blood dyscrasias
• Hepatic: Bilirubin no greater than 2.0 mg/dL; AST and ALT no greater than 4 times upper limit of normal (ULN); Albumin at least 3.0 g/dL; PT and PTT no greater than 1.5 times ULN; No liver failure
• Renal: Creatinine no greater than 1.7 mg/dL OR BUN no greater than 40 mg/dL; No renal failure
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No serious infection; No concurrent serious medical illness; No allergy to penicillin or history of serious reaction to penicillamine; No prior malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer

Alabama
      University of Alabama Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612,  United States
Georgia
      Emory University School of Medicine, Atlanta,  Georgia,  30322,  United States
Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
Michigan
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
North Carolina
      Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston Salem,  North Carolina,  27157-1082,  United States
Pennsylvania
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States
Texas
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284,  United States

Study chairs or principal investigators

Steven Brem,  Study Chair,  Johns Hopkins University   

Study ID Numbers:  CDR0000066872; JHOC-NABTT-9704
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003751
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08