Details
Description
Inclusion Criteria
Exclusion Criteria
Details
Title Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma. The CATNON Intergroup Trial.
IRB RTOG 0834
CC CC945
Hospital Main Campus
Stage N/A
Phase Phase 3
Disease Brain
Drug Temozolomide
Description
Primary objectives
- To assess whether concurrent radiotherapy with daily temozolomide chemotherapy improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.
- To assess whether adjuvant temozolomide chemotherapy improves survival as compared to no adjuvant temozolomide chemotherapy in patients with non-1p/19q deleted anaplastic glioma
Secondary objectives
- To assess whether concurrent and adjuvant temozolomide treatment 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 treatment on the quality of life in patients with non-1p/19q deleted anaplastic glioma.
Endpoints
- Primary endpoint: The primary endpoint of the study is overall survival, as measured from the day of randomization.
- Secondary endpoints: Secondary endpoints of the study are progression free survival, neurological deterioration free survival, quality of life, toxicity, and development of cognitive deterioration.
Inclusion Criteria
At the time of registration:
- Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic oligoastrocytoma or anaplastic astrocytoma by local diagnosis
- Availability of tumor material for central 1p/19q assessment, central MGMT promoter methylation assessment and central pathology review.
- Previous surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression
- WHO performance status 0-2
- Age ≥ 18 years
- All patients must use effective contraception if of reproductive potential. Females must not be pregnant or breast feeding
- Absence of known HIV infection, chronic hepatitis B or hepatitis C infection
- Absence of any other serious medical condition that can interfere with follow-up
- Absence of any medical condition which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction)
- Absence of previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in situ of the cervix and non-melanoma skin cancer.
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- No prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel®)
- No prior radiotherapy to the brain
- Before patient registration, written informed consent must be obtained, according to ICH/GCP, and national/local regulations.
Randomization step:
- The combination of :
- Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic oligoastrocytoma or anaplastic astrocytoma by local diagnosis AND
- Absence of combined 1p/19q loss
- Availability of tumor material for central 1p/19q assessment, central MGMT promoter methylation assessment and central pathology review
- WHO performance status 0-2
- Age ≥ 18 years
- Previous surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression
- Start of radiotherapy within 8 days from randomization
- Start of radiotherapy within 7 weeks (49 days) from surgery
- Patients must be on a stable or decreasing dose of steroids for at least two weeks
- No prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel®)
- No prior radiotherapy to the brain
- No concomitant treatment with other anti-cancer agents or with any other experimental agent
- Adequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days prior to randomization):
- neutrophils greater or equal to 1.5*109 cells/l
- platelets greater or equal to 100*109 cells/l
- bilirubin < 1.5 times upper limit of laboratory normal
- alkaline phosphatase, ASAT and ALAT < 2.5 times upper limit of laboratory normal
- serum creatinine lower than 1.5 times upper limit of laboratory normal
- All patients must use effective contraception if of reproductive potential. Females must not be pregnant or breast feeding
- Absence of known HIV infection, chronic hepatitis B or hepatitis C infection
- Absence of any other serious medical condition that could interfere with follow-up
- Absence of any medical condition which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction)
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
- Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable.