Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI NABTT-9704 JHOC-NABTT-9704, NCT00003751

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.

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:
 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

Expected Enrollment

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

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.

Brem S, Grossman SA, Carson KA, et al.: Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma. Neuro-oncol 7 (3): 246-53, 2005.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Steven Brem, MD, Protocol chair		Ph: 813-745-3063; 888-663-3488 Email: brem@moffitt.usf.edu

Registry Information
Official Title		Phase II Study of Penicillamine and Reduction of Copper for Angiosuppressive Therapy of Adults with Newly Diagnosed Glioblastoma
Trial Start Date		1999-03-25
Registered in ClinicalTrials.gov		NCT00003751
Date Submitted to PDQ		1999-01-13
Information Last Verified		2005-09-21
NCI Grant/Contract Number		CA062475

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