Phase III Trial of Anaplastic Glioma Without 1p/19q LOH - Full Text View

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: temozolomide Genetic: DNA methylation analysis Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: quality-of-life assessment Radiation: radiation therapy	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma. The CATNON Intergroup Trial.

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

Genetic and Rare Diseases Information Center resources: Oligodendroglioma Glioma Anaplastic Astrocytoma Anaplastic Oligodendroglioma

U.S. FDA Resources

Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:

Overall survival as measured from the day of randomization [ Time Frame: from randomisation till the date of death (assessed up to estimated 15 years from FPI) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: from randomization till the date of disease progression or death (assessed up to estimated 15 years from FPI) ] [ Designated as safety issue: No ]
Neurological deterioration-free survival [ Time Frame: from randomization till the date of neurological deterioration or death (assessed up to estimated 15 years from FPI) ] [ Designated as safety issue: No ]
Quality of life as assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 and the Brain Cancer Module-20 [ Time Frame: from 14 days prior to randomization till five years or death (assessed up to estimated 15 years from FPI) ] [ Designated as safety issue: No ]
Toxicity as measured by CTEP Active Version of CTCAE [ Time Frame: from randomization till disease progression or death (assessed up to estimated 15 years from FPI) ] [ Designated as safety issue: Yes ]
Development of cognitive deterioration as measured by the Mini Mental Status Exam [ Time Frame: from start RT till death (assessed up to estimated 15 years from FPI) ] [ Designated as safety issue: Yes ]


Enrollment:	751
Study Start Date:	December 2007
Estimated Primary Completion Date:	January 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: RT alone radiation therapy alone	Genetic: DNA methylation analysis MGMT methylation status is used for stratification at randomization. Other: laboratory biomarker analysis Prognostic factor analyses Procedure: quality-of-life assessment Quality of Life analysis will also be used to assess neurological deterioration free progression Radiation: radiation therapy Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule
Active Comparator: RT & Concurrent CT Radiotherapy and concurrent temozolomide chemotherapy	Drug: temozolomide Patients randomized to concomitant temozolomide will receive temozolomide continuously at a daily dose of 75 mg/m² during radiotherapy. Other Names: Temodar Temodal Temcad Genetic: DNA methylation analysis MGMT methylation status is used for stratification at randomization. Other: laboratory biomarker analysis Prognostic factor analyses Procedure: quality-of-life assessment Quality of Life analysis will also be used to assess neurological deterioration free progression Radiation: radiation therapy Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule
Active Comparator: RT + Adjuvant CT Radiotherapy plus adjuvant temozolomide chemotherapy	Drug: temozolomide Patients randomized to concomitant temozolomide will receive temozolomide continuously at a daily dose of 75 mg/m² during radiotherapy. Other Names: Temodar Temodal Temcad Genetic: DNA methylation analysis MGMT methylation status is used for stratification at randomization. Other: laboratory biomarker analysis Prognostic factor analyses Procedure: adjuvant therapy Patients randomized to adjuvant temozolomide will start adjuvant temozolomide after a 4 week resting period after the end of radiotherapy. Procedure: quality-of-life assessment Quality of Life analysis will also be used to assess neurological deterioration free progression Radiation: radiation therapy Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule
Active Comparator: RT & Concurrent CT + adjuvant CT Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy	Drug: temozolomide Patients randomized to concomitant temozolomide will receive temozolomide continuously at a daily dose of 75 mg/m² during radiotherapy. Other Names: Temodar Temodal Temcad Genetic: DNA methylation analysis MGMT methylation status is used for stratification at randomization. Other: laboratory biomarker analysis Prognostic factor analyses Procedure: adjuvant therapy Patients randomized to adjuvant temozolomide will start adjuvant temozolomide after a 4 week resting period after the end of radiotherapy. Procedure: quality-of-life assessment Quality of Life analysis will also be used to assess neurological deterioration free progression Radiation: radiation therapy Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule

Detailed Description:

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.

OUTLINE: 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 for 5 years.

Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis.

After completion of study treatment, patients are followed every 3 months.

Eligibility


Ages Eligible for Study:	18 Years to 120 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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, isocitrate dehydrogenase mutation analysis, and central pathology review
Patients must be on a stable or decreasing dose of steroids for at least two weeks prior to randomization

PATIENT CHARACTERISTICS:

WHO performance status 0-2
ANC ≥ 1.5 x 10^9 cells/L
Platelet count ≥ 100 x 10^9 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 other prior malignancies except for any malignancy which was treated with curative intent more than 5 years prior to registration and adequately controlled limited basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
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

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626990

Show 132 Study Locations

Sponsors and Collaborators

European Organisation for Research and Treatment of Cancer - EORTC

NCIC Clinical Trials Group

Radiation Therapy Oncology Group

Medical Research Council

Cooperative Trials Group for Neuro-Oncology

Merck Sharp & Dohme Corp.

Investigators


Study Chair:	Wolfgang Wick	Universitatsklinikum Heidelberg
Study Chair:	Warren P. Mason, MD	Princess Margaret Hospital, Canada
Study Chair:	Michael A. Vogelbaum, MD, PhD	The Cleveland Clinic
Study Chair:	S. Erridge	Medical Research Council
Study Chair:	Anna Nowak, MD	Sir Charles Gairdner Hospital - Nedlands

More Information


Responsible Party:	European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:	NCT00626990 History of Changes
Other Study ID Numbers:	EORTC-26053-22054 NCIC CTG CEC.1 RTOG-0834 2006-001533-17 P04839 MRC BR14
Study First Received:	February 28, 2008
Last Updated:	February 9, 2016
Health Authority:	Australia: National Health and Medical Research Council Austria: Agency for Health and Food Safety Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Italy: Ethics Committee Israel: Ethics Commission Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Spain: Agencia Española de Medicamentos y Productos Sanitarios Switzerland: Swissmedic Turkey: Ethics Committee United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:


adult anaplastic oligodendroglioma adult anaplastic astrocytoma

Additional relevant MeSH terms:


Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Neoplasms Nervous System Diseases Temozolomide	Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

ClinicalTrials.gov processed this record on September 27, 2016

Phase III Trial of Anaplastic Glioma Without 1p/19q LOH (CATNON)