Penicillamine, Low Copper Diet, and Radiation Therapy in Treating Patients With Glioblastoma

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00003751

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: penicillamine Radiation: radiation therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Primary Purpose:

Treatment

Official Title:

Phase II Study of Penicillamine and Reduction of Copper for Angiosuppressive Therapy of Adults With Newly Diagnosed Glioblastoma

Study Start Date :

Mar 1, 1999

Actual Primary Completion Date :

Jun 1, 2004

Actual Study Completion Date :

Jul 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
3	Emory University School of Medicine	Atlanta	Georgia	United States	30322
4	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21287
5	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
6	Henry Ford Hospital	Detroit	Michigan	United States	48202
7	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
8	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
9	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284