Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma. The CATNON Intergroup Trial.
Overview
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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether giving temozolomide during and/or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma.
This randomized phase III trial is studying giving temozolomide during and/or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma.
Basic Trial Information
| Phase | Type | Status | Age | Protocol ID(s) |
|---|---|---|---|---|
| III | Treatment | Active On-going | 18+ | EORTC-26053 (RTOG 0834) |
|
Cancer Types Brain Tumor, Adult |
||||
Basic Trial Description
Patients will be randomly assigned (have an equal chance of being placed) to one of four treatment groups.
Patients in group one will undergo radiation therapy once a day, 5 days a week for 6½ weeks.
Patients in group two will undergo radiation therapy once a day, 5 days a week and receive temozolomide by mouth once a day for 6½ weeks.
Patients in group three will undergo radiation therapy once a day, 5 days a week for 6½ weeks. Four weeks after finishing radiation therapy, they will receive temozolomide by mouth once a day for 5 days. Treatment with temozolomide may repeat every 4 weeks for up to twelve courses.
Patients in group four will undergo radiation therapy once a day, 5 days a week and receive temozolomide by mouth once a day for 6½ weeks. Four weeks after finishing radiation therapy and temozolomide, they will receive temozolomide by mouth once a day for 5 days. Treatment with temozolomide may repeat every 4 weeks for up to twelve courses.
Patients will fill out quality of life questionnaires at the beginning of the study, 4 weeks after finishing radiation therapy, and every 3 months thereafter.
Tissue samples will be collected at the beginning of the study for laboratory studies.
After finishing treatment, patients will be evaluated every 3 months.
Medical Professionals
Objectives
Primary
- To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.
- To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.
Secondary
- To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.
- To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.
- To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.
This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs > 0), age (≤ 50 vs > 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients undergo radiotherapy* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions).
- Arm II: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy).
- Arm III: Patients undergo radiotherapy* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.
- Arm IV: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.
[Note: *Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery.]
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients complete quality-of-life questionnaires, including QLQ-C30 version 3, BCM20, and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months thereafter.
Tissue samples are collected at baseline for histology review, 1p/19q analysis, and methylation status of the O6-methylguanine-DNA methyltransferase promoter.
After completion of study treatment, patients are followed every 3 months.
For more details about this trial, refer to the Health Professional version of the trial summary.
Explanation of Eligibility Criteria
- Histologically confirmed diagnosis of 1 of the following:
- Anaplastic oligodendroglioma
- Anaplastic oligoastrocytoma
- Anaplastic astrocytoma
- Newly diagnosed disease
- Prior surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression
- Absence of combined 1p/19q loss Tumor material available for central 1p/19q assessment, central O6-methylguanine-DNA methyltransferase promoter methylation status assessment, and central pathology review
- Patients must be on a stable or decreasing dose of steroids for at least two weeks prior to randomization Prior/Concurrent Therapy:
- See Disease Characteristics
- No prior chemotherapy, including carmustine-containing wafers (Gliadel®)
- No prior radiotherapy to the brain
- No concurrent growth factors unless vital for the patient
- No other concurrent investigational treatment
- No other concurrent anticancer agents
Patient Characteristics:
- WHO performance status 0-2
- ANC ≥ 1.5 x 109 cells/L
- Platelet count ≥ 100 x 109 cells/L
- Bilirubin < 1.5 x upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 x ULN
- AST and ALT < 2.5 x ULN
- Serum creatinine < 1.5 x ULN
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No known HIV infection or chronic hepatitis B or hepatitis C infection
- No other serious medical condition that would interfere with follow-up
- No medical condition that could interfere with oral medication intake (e.g., frequent vomiting or partial bowel obstruction)
- No prior or concurrent malignancies at other sites except for surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer
- No psychological, familial, sociological, or geographical condition that would potentially hamper compliance with the study protocol and follow-up schedule
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please call our Clinical Research Center at 407.303.2059 for additional information.
Our Web site gives a description of the clinical trials offered at the FHCI. Read over the information carefully and fully consider all of your options. Because trials can frequently change, call our Clinical Research Center at 407.303.2059 for the most up-to-date information. Please reference the protocol number (listed on the top of this page under Study Summary) when inquiring about a clinical trial.
