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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003751
• Other study ID #: NABTT-9704 CDR0000066872
• Secondary ID: U01CA062475NABTT
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: May 1, 2012
• Start date: March 1999
• Est. completion date: July 2005

Study information

• Verified date: May 2012
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2005
• Est. primary completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• penicillamine

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation