Clinical trial NCT00003751: Penicillamine, Low Copper Diet, and Radiation Therapy in Treating Patients With Glioblastoma
Official title: Phase II Study of Penicillamine and Reduction of Copper for Angiosuppressive Therapy of Adults With Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-08-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: OBJECTIVES: I. Determine the effect of penicillamine and copper reduction 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.

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 month (with MRI every 2 months) until death.

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

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven supratentorial grade IV astrocytoma (glioblastoma multiforme)

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 2 months 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

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Steven Brem, MD
role: STUDY_CHAIR
References:
citation: Brem S, Grossman SA, Carson KA, New P, Phuphanich S, Alavi JB, Mikkelsen T, Fisher JD; New Approaches to Brain Tumor Therapy CNS Consortium. Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma. Neuro Oncol. 2005 Jul;7(3):246-53. doi: 10.1215/S1152851704000869.
citation: Brem S, Grossman SA, New P, et al.: Phase II study of penicillamine and reduction of copper, for angiosuppressive therapy of glioblastoma: preliminary safety and feasibility study. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A-666, 2000.