Thalidomide and Procarbazine in Treating Patients With Recurrent or Progressive Malignant Glioma

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: procarbazine hydrochloride (Drug); thalidomide (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Wake Forest University

Official(s) and/or principal investigator(s):
Glenn J. Lesser, MD, Study Chair, Affiliation: Wake Forest University
Edward G. Shaw, MD, Affiliation: Wake Forest University
Volker W. Stieber, MD, Affiliation: Wake Forest University

RATIONALE: Thalidomide may stop the growth of malignant glioma by stopping blood flow to the tumor. Drugs used in chemotherapy, such as procarbazine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with procarbazine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving thalidomide together with procarbazine works in treating patients with recurrent or progressive malignant glioma.

Official title: A Phase II Trial Of Thalidomide And Procarbazine In Adults With Recurrent/Progressive Gliomas

Study design: Treatment, Open Label

Primary outcome: Response rate by CT scan and MRI at baseline, pre-odd cycles, and study completion

Secondary outcome:

Progression-free survival by CT scan, MRI, and follow up form at baseline, pre-odd cycles, and study completion

Overall survival by follow-up form at study completion

Quality of life by FACT-Br, FACIT-F and Karnofsky performance status (PS) at baseline, pre-odd cycles, and study completion

Toxicity by evaluation form at baseline, pre-odd cycles, and study completion

Detailed description: OBJECTIVES:

Primary

- Determine the response rate in patients with recurrent or progressive malignant glioma

treated with thalidomide and procarbazine.

Secondary

- Determine the progression-free survival of patients treated with this regimen.

- Determine the overall survival of patients treated with this regimen.

- Determine the quality of life of patients treated with this regimen.

- Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral procarbazine once daily on days 1-5 and oral thalidomide once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then before every odd course.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 23-55 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant glioma

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Glioblastoma multiforme

- Anaplastic mixed oligoastrocytoma

- Progressive or recurrent disease* after radiotherapy with or without chemotherapy

NOTE: *Patients with prior low-grade glioma who progressed after therapy and are found to have high-grade glioma are eligible

- Measurable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 2 months

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin ≤ 1. 5 mg/dL

- Transaminases ≤ 4 times upper limit of normal

Renal

- Creatinine ≤ 1. 7 mg/dL

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 1 highly active method and 1 additional effective method of

contraception for 1 month before, during, and for 4 weeks after study treatment

- No concurrent serious infection

- No other concurrent medical illness that would preclude study treatment

- No other malignancy within the past 5 years except curatively treated carcinoma in

situ of the cervix or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior thalidomide

- No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy

- See Disease Characteristics

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- No prior procarbazine

- No more than 2 prior chemotherapy regimens for malignant glioma

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- At least 3 months since prior radiotherapy

Other

- Recovered from prior therapy

- More than 7 days since prior antidepressants (selective serotonin reuptake inhibitors

and/or monamine oxidase inhibitors)

- No concurrent antidepressants

- No other concurrent investigational agents

CCOP - Central Illinois, Decatur, Illinois 62526, United States

CCOP - Southeast Cancer Control Consortium, Goldsboro, North Carolina 27534-9479, United States

Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States

CCOP - Greenville, Greenville, South Carolina 29615, United States

CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States

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

Starting date: January 2004
Last updated: May 23, 2008