Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Oligodendroglioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Vincristine

Lomustine

Procarbazine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.

concomitant temozolomide (TMZ)

radiotherapy

procarbazine

adjuvant temozolomide (TMZ)

CCNU

vincristine

Kurt Jaeckle, MD

Site Public Contact

John B. Fiveash

Alison K. Conlin

Kelly Braun

Richard M. Green

David E. Piccioni

Xiao-Tang Kong

Christopher U. Jones

Orwa Aboud

Shahzad Siddique

Nadine G. Mikhaeel-Kamel

Nicholas A. Blondin

Matthias Holdhoff

Harold Richter

Ashley P. Ghiaseddin

Kurt A. Jaeckle

Sherif Makar

Alfredo D. Voloschin

Lisa Sudmeier

John M. Schallenkamp

Bryan A. Faller

Stefania Maraka

Anupama Chundury

Richard L. Deming

Joshua Lukenbill

Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

This study will be a randomized phase III for patients with newly diagnosed co-deleted 1p/19q anaplastic glioma or high risk low grade glioma. The trial will only enroll patients with 1p/19q co-deletion. This study includes two arms as described in the "Arms" section. A dynamic allocation procedure will be used to allocate an equal number of patients to different arms (Arms A:B = 1:1). This procedure will balance the marginal distributions of the stratification factors among arms. The stratification factors that will be used are cooperative groups (EORTC vs. all North American groups), age (≤ 50 vs. \> 50), performance score (ECOG 0-1 vs. 2), and tumor grade (anaplastic glioma vs. low grade glioma).

The primary goal is to determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --\> TMZ) (Arm B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by PCV chemotherapy (RT --\> PCV)(Arm A).

Secondary Goals:

1. Time to Progression - To determine whether patients who receive (RT + TMZ --\> TMZ) have a significantly longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT --\> PCV).
2. Correlation between exploratory biomarkers and survival - To determine whether there is a difference in survival based on t(1;19)(q10, p10) translocation status and MGMT promoter hypermethylation status.
3. Descriptive Comparisons of Additional Secondary Endpoints - To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
4. Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons.
5. Neurocognitive and Quality of Life (QOL) Effects - To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints.
6. Banking of Biospecimens and Neuroimaging Studies - To store blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations.

After completion of study treatment, patients are followed every 12 weeks for 1 year, then every 4 months for 2 years and then every 6 months until progressive disease or until the end of study participation.

Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma

Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma

The distribution of progression free survival for Arms A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median progression free survival (PFS) will be estimated with their confidence intervals. The Cox proportional hazards model will be used to assess whether the distributions of progression survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and performance score). Both non-inferiority and superiority will be tested in this trial for the primary goal and no multiple-comparison adjustment will be considered.

Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. Correlations among baseline neurocognitive test scores and progression free survival will be analyzed using Cox proportional hazards model.

Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. For each test in the battery, a standard error of measurement will be used to derive the Reliable Change Index (RCI) which will be used to represent the 90% confidence interval for the difference in raw scores from baseline to follow-up assessment will be coded as 1 (deterioration), 2 (no change), and 3 (improved) according to the RCI.

The Cox proportional hazards model will be used to assess whether the distributions of overall survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and Performance Score). The distribution of overall survival for Arm A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median survivals will be estimated with their 95% confidence intervals.

Summarized for each arm and compared between the arms using the Chi square test.

The maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. In addition, will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and treatment-related adverse events will be evaluated using all patients. Treatment-related adverse events will be tabulated for each arm.

National Cancer Institute (NCI)

European Organisation for Research and Treatment Center (EORTC)

Canadian Cancer Trials Group

Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for concomitant temozolomide (tmz)