Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Tamoxifen and Bortezomib in Treating Patients With Recurrent Gliomas

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over NCI NCI-05-C-0137 NCT00112762

Special Category: NIH Clinical Center trial

Objectives

1. Determine the antitumor activity of tamoxifen and bortezomib in patients with recurrent high-grade gliomas.
2. Determine, preliminarily, the toxic effects of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed high-grade glioma, including any of the following:
  • Glioblastoma multiforme and its variants (e.g., gliosarcoma)
  • Anaplastic glioma, including any of the following types:
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Anaplastic mixed oligoastrocytoma
    • Malignant astrocytoma or glioma not otherwise specified
    • Brainstem glioma by radiography or clinical diagnosis



• Unequivocal evidence of tumor progression by MRI or CT scan while on a steroid dosage that has been stable for ≥ 5 days



• Patients who have undergone prior surgical resection of recurrent or progressive tumor must have subsequent residual disease



• Failed prior radiotherapy



• No documented tumor progression during prior treatment with tamoxifen

Prior/Concurrent Therapy:

Biologic therapy

• At least 1 week since prior interferon or thalidomide
• No concurrent immunotherapy

Chemotherapy

• At least 2 weeks since prior vincristine
• At least 6 weeks since prior nitrosoureas
• At least 3 weeks since prior procarbazine
• No concurrent standard anticancer chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 6 months since prior tamoxifen

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior and no concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• Recovered from all prior therapy
• At least 4 weeks since prior and no concurrent investigational agents
• At least 4 weeks since prior cytotoxic therapy
• At least 1 week since other prior noncytotoxic agents (e.g., isotretinoin) except radiosensitizers
• No concurrent enzyme-inducing anti-epileptic drugs (e.g., phenytoin, phenobarbital, or carbamazepine)

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dL (transfusion allowed)

Hepatic

• SGOT < 2 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• No hepatocellular and/or cholestatic dysfunction by liver biopsy, liver ultrasound, or liver function tests
• No other hepatic disease

Renal

• Creatinine < 1.5 mg/dL

  AND/OR

• Creatinine clearance ≥ 60 mL/min
• No renal disease by renal biopsy, ultrasound, MRI, CT scan, or blood test

Cardiovascular

• No coronary artery disease
• No congestive heart failure
• No arrhythmia requiring medication
• No other significant active cardiac disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception during and for 2 months after study participation
• Able to swallow tamoxifen tablets
• No other significant uncontrolled medical illness that would preclude study participation
• No significant severe psychiatric disease that requires hospitalization or would preclude study compliance
• No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active infection requiring IV antibiotics
• No other disease that would obscure study drug toxicity or dangerously alter drug metabolism
• No peripheral neuropathy ≥ grade 2

Expected Enrollment

A total of 46-76 patients (27-40 in stratum 1 and 19-36 in stratum 2) will be accrued for this study within 2 years.

Outcomes

Response, defined as stable disease or objective (partial or complete) response

Outline

Patients are stratified according to disease (glioblastoma multiforme vs anaplastic glioma).

Patients receive oral tamoxifen twice daily on days 1-42 and bortezomib IV on days 3, 6, 10, 13, 24, 27, 31, and 34. Treatment repeats every 42 days for up to 9 courses in the absence of disease progression or unacceptable toxicity. After 9 courses of treatment, patients who continue to benefit from study treatment and who experience no unacceptable toxicity may receive additional courses of treatment at the investigator's discretion.

After completion of study treatment, patients are followed within 2 weeks.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Howard Fine, MD, Protocol chair		Ph: 301-402-6298

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Web site for additional information

Registry Information
Official Title		Phase II Trial of Tamoxifen and Bortezomib in Patients With Recurrent High-Grade Gliomas
Trial Start Date		2005-06-01
Trial Completion Date		2010-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00112762
Date Submitted to PDQ		2005-04-14
Information Last Verified		2008-10-24

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