Temozolomide & RT Followed by Dose Dense vs Temozolomide & Retinoic Acid in Pts w/Glioblastoma

Condition(s) targeted: Glioblastoma; Gliomas

Intervention: Temozolomide (Drug); Temozolomide (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Memorial Sloan Kettering Cancer Center

Official(s) and/or principal investigator(s):
Lisa DeAngelis, M.D, Principal Investigator, Affiliation: Memorial Sloan Kettering Cancer Center

Patients have a newly diagnosed brain tumor called a malignant glioma and participate in the study to see if it is possible to increase the benefit of temozolomide when given after radiation. A recent study showed that patients with newly diagnosed glioblastoma lived longer when treated with both temozolomide and radiotherapy followed by 6 months of temozolomide than patients treated with radiotherapy alone. Patients will receive standard low dose temozolomide during radiation. After radiation, they will be randomized to receive either more intense temozolomide or continuous low dose temozolomide.

Official title: A Randomized Phase II Trial of Concurrent Temozolomide and Radiotherapy Followed by Dose Dense Versus Metronomic Temozolomide and Maintenance Cis-Retinoic Acid for Patients With Newly Diagnosed Glioblastoma and Other Malignant Gliomas

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To determine the overall survival of patients with newly diagnosed glioblastoma multiforme treated with concurrent temozolomide and radiotherapy followed by dose dense or metronomic dosing of temozolomide and maintenance cis-retinoic acid.

Secondary outcome:

Progression free survival

To evaluate the prognostic impact of methylated MGMT status.

To collect preliminary data on the efficacy of this regimen and impact of MGMT status in other malignant glioma subtypes.

Detailed description: This is a randomized phase II study that will test two different adjuvant temozolomide regimens in patients with newly diagnosed glioblastoma multiforme. The goal of this study is to identify a regimen that would be appropriate to bring to a phase III trial and compare to the standard dosing regimen of temozolomide recently reported by Stupp et al. in the New England Journal of Medicine. Secondary goals of this study include: prospective analysis of the prognostic impact of MGMT status and generation of preliminary data regarding this treatment strategy for other types of malignant glioma. The decision regarding which treatment patients receive is made randomly. Neither them or their doctor can select which treatment the patient will receive. There is reason to believe that both of these doses may benefit treating your brain tumor. After 6 months of chemotherapy, and assuming the brain tumor has not shown any sign of growth, they will begin receiving cis-retinoic acid. Cis retinoic acid has been shown in one study to possibly prevent or delay tumor recurrence.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Pathologic evidence of a malignant glioma.

- Tissue block or unstained slides must be available for MGMT analysis.

- Age 18-70

- KPS > 50

- Granulocyte count >1. 5 X 109/L

- Platelet count >99 X 109/L

- SGOT < 2. 5X upper limit of normal (ULN).

- Serum creatinine < 2X ULN.

- Bilirubin < 2X ULN.

- All patients must sign written informed consent.

Exclusion Criteria:

- Any prior chemotherapy, radiotherapy and biologic therapy for glioma.

- Any prior experimental therapy for glioma.

- Other concurrent active malignancy (with the exception of cervical carcinoma in situ

or basal cell ca of the skin).

- Serious medical or psychiatric illness that would in the opinion of the investigator

would interfere with the prescribed treatment.

- Pregnant or breast feeding women.

- Refusal to use effective contraception.

Memorial Sloan-Kettering at Basking Ridge, Basking Ridge, New Jersey 07920, United States

Memorial Sloan-Kettering Cancer Center at Commack, Commack, New York 11725, United States

Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States

Memorial Sloan-Kettering Cancer Center

Starting date: August 2005
Last updated: November 21, 2014