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

Primary Purpose

Brain and Central Nervous System Tumors

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

temozolomide

DNA methylation analysis

laboratory biomarker analysis

adjuvant therapy

quality-of-life assessment

radiation therapy

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult anaplastic oligodendroglioma, adult anaplastic astrocytoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arizona Oncology Services Foundation
Cedars-Sinai Medical Center
UCSF University of California San Francisco Medical Center-Mount Zion
University of Florida
Mayo Clinic in Florida
Florida Hospital
Emory University
Memorial Health University Medical Center
Northwestern University
Loyola University Medical Center
Oncology Associates PC
Parkview Hospital
Saint Vincent Oncology Center
McFarland Clinic
June E. Nylen Cancer Center
Via Christi Regional Medical Center
Wesley Medical Center
Maine Medical Center
Boston Medical Center
Brigham and Women's Hospital
Massachussets General Hospital Cancer Center
Saint Joseph Mercy Hospital
Henry Ford Hospital
West Michigan Cancer Center
St John's Mercy Medical Center
Methodist Estabrook Cancer Center
Dartmouth Hitchcock Medical Center
State University of New York Upstate Medical University
Highland Hospital
University of Rochester - James P. Wilmot Cancer Center
Carolinas Medical Center
Akron City Hospital - Summa Health System
Summa Barberton Hospital
Cleveland Clinic Foundation
MetroHealth Medical Center
Western Reserve University
Ohio State University Medical Center
Southwest General Health Center Ireland Cancer Center
UHHS-Chagrin Highlands Medical Center
Cancer Care Center, Incorporated
UHHS - Westlake Medical Center
Cancer Treatment Center
Abington Memorial Hospital
Lehigh Valley Hospital
UPMC - Heritage Valley Health System - The Medical Center
Penn State M.S. Hershey Medical Center
Thomas Jefferson University Hospital
Reading Hospital and Medical Center
Medical University of South Carolina
Cancer Centers of the Carolinas - Eastside
Cancer Centers of the Carolinas - Faris Road
Cancer Centers of the Carolinas - Greer Radiation Oncology
Cancer Centers of the Carolinas - Seneca
Spartanburg Regional Medical Center
Rapid City Regional Hospital
University of Texas Medical Branch
Md Anderson Cancer Center
Methodist Hospital
Intermountain Medical Center
Utah Valley Regional Medical Center
Dixie Medical Center Regional Cancer Center
LDS Hospital
University Of Utah - Huntsman Cancer Institute
Virginia Commonwealth University
Swedish Cancer Institute
Virginia Mason CCOP
Saint Mary's Hospital
Saint Vincent Hospital
Gundersen Lutheran
University Of Wisconsin Comprehensive Cancer Center
Froedtert and the Medical College of Wisconsin
Waukesha Memorial Hospital
Royal North Shore Hospital
Royal Prince Alfred Hospital
Princess Alexandra Hospital
Royal Melbourne Hospital
Flinders Medical Centre
Austin-Repatriation Medical Centre
Royal Hobart Hospital
St Vincent'S Hospital
Sir Charles Gairdner Hospital
Alfred Hospital
ZNA Middelheim
Cliniques Universitaires St. Luc
Universitair Ziekenhuis Brussel
Clinique Notre-Dame
Algemeen Ziekenhuis Sint Lucas
U.Z. Gasthuisberg
Tom Baker Cancer Centre
London Regional Cancer Center
Allan Blair Cancer Centre
University Health Network - Oci / Princess Margaret Hospital
Cancercare Manitoba
Assistance Publique - Hôpitaux de Marseille - C.H.U. De La Timone
C.H.U. de Nancy - Hopital St Julien
Centre Antoine Lacassagne
Chu Pitie-Salpetriere AP-HP
Centre Eugene Marquis
Institut Gustave Roussy
Klinikum Bamberg
Universitaetsklinikum Bonn
Medizinische Hochschule Hannover
UniversitaetsKlinikum Heidelberg
Universitaetskliniken Regensburg
Universitaetsklinikum Tuebingen
Tel Aviv Sourasky Medical Center
Ospedale Bellaria
Istituto Scientifico H.S. Raffaele
Azienda Ospedaliera San Giovanni Battista Di Torino-Universita Di Torino
Academisch Medisch Centrum - Universiteit van Amsterdam
Vrije Universiteit Medisch Centrum
Medisch Centrum Haaglanden - Westeinde
University Medical Center Groningen
Maastro Clinic - Maastricht Radiation Oncology
Radboud University Nijmegen Medical Centre
Erasmus MC - Daniel den Hoed Cancer Center
Hospital Clinic Universitari
ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
Hopital Cantonal Universitaire De Geneve
Universitaetsspital
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Addenbrookes Hospital
Cheltenham General Hospital
Western General Hospital
Royal Devon And Exeter Hospital
St. James'S University Hospital
Christie NHS Foundation Trust
Nottingham University Hospitals NHS Trust - City Hospital campus
Derriford Hospital
Weston Park Hospital
Royal Marsden Hospital
Clatterbridge Centre for Oncology NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Arm Label

Radiotherapy (RT) alone

RT & Concurrent CT

RT + Adjuvant CT

RT & Concurrent CT + adjuvant CT

Arm Description

radiation therapy alone

Radiotherapy and concurrent temozolomide chemotherapy

Radiotherapy plus adjuvant temozolomide chemotherapy

Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy

Outcomes

Primary Outcome Measures

Overall Survival as Measured From the Day of Randomization

The duration of survival is the time interval between randomization and the date of death due to any cause. Patients not reported dead or lost to follow up will be censored at the date of the last follow up examination.

Secondary Outcome Measures

Progression-free Survival

Disease progression is defined as radiological or neurological/clinical progression (whichever occurs first); progression free survival (PFS) is the time interval between the date of randomization and the date of disease progression or death whichever occurs first. If neither event has been observed, the patient is censored at the date of the last follow up examination. Radiological progression was defined as increase of contrast enhancing area on MRI or CT scans of more than 25% as measured by two perpendicular diameters compared to the smallest measurements ever recorded for the same lesion by the same technique. The appearance of new lesions with or without contrast enhancement Neurological/clinical progression was defined as:decrease in WHO performance status,deterioration of neurological functions,appearance of signs/symptoms of increased intracranial pressure,and/or start of corticosteroid or increase of corticosteroid dosage by 50% for control of neurological symptoms.

Quality of Life of the Patient

Quality of life was assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 and the Brain Cancer Module-20

Neurological Deterioration Free Survival

Neurological deterioration is defined as a decrease in WHO performance status as follows: decrease in WHO performance status for patients with baseline WHO performance status 0: deterioration to WHO performance status 2 or worse for which no other explanation is present, and which is maintained for at least three months for patients with baseline WHO performance status 1 or 2: deterioration to WHO performance status 3 or worse for which no other explanation is present and which is maintained for at least three months The date of neurological deterioration will be the first date the persistent decrease in performance status was diagnosed. Neurological deterioration free progression is the time interval between the date of randomization and the date of neurological deterioration or death whichever occurs first. If neither event has been observed, the patient is censored at the date of the last follow up examination

Full Information

NCT ID

NCT00626990

First Posted

February 28, 2008

Last Updated

August 30, 2023

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

NCIC Clinical Trials Group, Radiation Therapy Oncology Group, Medical Research Council, Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00626990

Brief Title

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

Acronym

CATNON

Official Title

Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma. The CATNON Intergroup Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 2007 (Actual)

Primary Completion Date

September 5, 2018 (Actual)

Study Completion Date

December 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

NCIC Clinical Trials Group, Radiation Therapy Oncology Group, Medical Research Council, Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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, World Health Organization (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. 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 EORTC core quality of life questionnaire (QLQ-C30) version 3, EORTC brain cancer module (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain and Central Nervous System Tumors

Keywords

adult anaplastic oligodendroglioma, adult anaplastic astrocytoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

751 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radiotherapy (RT) alone

Arm Type

Active Comparator

Arm Description

radiation therapy alone

Arm Title

RT & Concurrent CT

Arm Type

Active Comparator

Arm Description

Radiotherapy and concurrent temozolomide chemotherapy

Arm Title

RT + Adjuvant CT

Arm Type

Active Comparator

Arm Description

Radiotherapy plus adjuvant temozolomide chemotherapy

Arm Title

RT & Concurrent CT + adjuvant CT

Arm Type

Active Comparator

Arm Description

Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy

Intervention Type

Drug

Intervention Name(s)

temozolomide

Other Intervention Name(s)

Temodar, Temodal

Intervention Description

Patients randomized to concomitant temozolomide will receive temozolomide continuously at a daily dose of 75 mg/m² during radiotherapy.

Intervention Type

Genetic

Intervention Name(s)

DNA methylation analysis

Intervention Description

O6-Methylguanine-DNA Methyltransferase (MGMT) methylation status is used for stratification at randomization.

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Prognostic factor analyses

Intervention Type

Procedure

Intervention Name(s)

adjuvant therapy

Intervention Description

Patients randomized to adjuvant temozolomide will start adjuvant temozolomide after a 4 week resting period after the end of radiotherapy.

Intervention Type

Procedure

Intervention Name(s)

quality-of-life assessment

Intervention Description

Quality of Life analysis will also be used to assess neurological deterioration free progression

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Intervention Description

Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule

Primary Outcome Measure Information:

Title

Overall Survival as Measured From the Day of Randomization

Description

Time Frame

from date from enrollment till the date of death (time till death is up to 10.9 years after patient enrollment in the study)

Secondary Outcome Measure Information:

Title

Progression-free Survival

Description

Time Frame

from randomization till the date of disease progression or death (time till death is up to 10.9 years after patient enrollment in the study)

Title

Quality of Life of the Patient

Description

Quality of life was 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 (time till death is up to 10.9 years after patient enrollment in the study)

Title

Neurological Deterioration Free Survival

Description

Time Frame

within 2 weeks of randomization; during radiotherapy at week 4 and 6; 4 weeks after the end of radiotherapy; Six monthly after the end of radiotherapy; Prior to each cycle of adjuvant therapy; Every six months after the documentation of first progression.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility 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 Absolute Neutrophil Count (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 Aspartate Aminotransferase (AST) and Alanine Aminotransferase (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

Overall Study Officials: