Official Title: “Phase II Trial of Tamoxifen and Bortezomib in Patients With Recurrent High-Grade Gliomas”

RATIONALE: Drugs used in chemotherapy, such as tamoxifen, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving tamoxifen together with bortezomib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving tamoxifen together with bortezomib works in treating patients with recurrent gliomas.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: December 2010

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

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.

PROJECTED ACCRUAL: 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.

Intervention(s) in this Clinical Trial

• Drug: bortezomib
• Drug: tamoxifen citrate

Primary Measures

• Response, defined as stable disease or objective (partial or complete) response
  • Safety Issue?: No

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

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• Karnofsky 60-100%
• Life expectancy
• More than 8 weeks
• Hematopoietic
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• 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

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

Howard A. Fine, MD Study Chair NCI - Neuro-Oncology Branch  

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00112762

Study ID Number: CDR0000429542

ClinicalTrials.gov Identifier: NCT00112762

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database

Web site for additional information