Clinical trial NCT00626990: Phase III Trial of Anaplastic Glioma Without 1p/19q Loss of Heterozygosity (LOH)
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Brain and Central Nervous System Tumors
Keywords: adult anaplastic oligodendroglioma
adult anaplastic astrocytoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: NCIC Clinical Trials Group
name: Radiation Therapy Oncology Group
name: Medical Research Council
name: Merck Sharp & Dohme LLC
First posted: 2008-02-29
Enrollment: 751
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival as Measured From the Day of Randomization
timeFrame: 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 outcomes:
measure: Progression-free Survival
timeFrame: 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)
measure: Quality of Life of the Patient
timeFrame: 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)
measure: Neurological Deterioration Free Survival
timeFrame: 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.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF University of California San Francisco Medical Center-Mount Zion
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Oncology Associates PC
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Oncology Center
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Sioux City
country: United States
facility: June E. Nylen Cancer Center
state: Iowa
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Scarborough
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachussets General Hospital Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: St John's Mercy Medical Center
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Rochester
country: United States
facility: Highland Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester - James P. Wilmot Cancer Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron City Hospital - Summa Health System
state: Ohio
city: Barberton
country: United States
facility: Summa Barberton Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Southwest General Health Center Ireland Cancer Center
state: Ohio
city: Orange Village
country: United States
facility: UHHS-Chagrin Highlands Medical Center
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Westlake
country: United States
facility: UHHS - Westlake Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Beaver
country: United States
facility: UPMC - Heritage Valley Health System - The Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State M.S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Eastside
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Faris Road
state: South Carolina
city: Greer
country: United States
facility: Cancer Centers of the Carolinas - Greer Radiation Oncology
state: South Carolina
city: Seneca
country: United States
facility: Cancer Centers of the Carolinas - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Saint George
country: United States
facility: Dixie Medical Center Regional Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University Of Utah - Huntsman Cancer Institute
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Virginia Mason CCOP
state: Washington
city: Green Bay
country: United States
facility: Saint Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran
state: Wisconsin
city: Madison
country: United States
facility: University Of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Heidelberg
country: Australia
facility: Austin-Repatriation Medical Centre
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Melbourne
country: Australia
facility: St Vincent'S Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Prahran
country: Australia
facility: Alfred Hospital
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: Cliniques Universitaires St. Luc
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Charleroi
country: Belgium
facility: Clinique Notre-Dame
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Sint Lucas
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: London
country: Canada
facility: London Regional Cancer Center
city: Saskatoon
country: Canada
facility: Allan Blair Cancer Centre
city: Toronto
country: Canada
facility: University Health Network - Oci / Princess Margaret Hospital
city: Winnipeg
country: Canada
facility: Cancercare Manitoba
city: Marseille
country: France
facility: Assistance Publique - Hôpitaux de Marseille - C.H.U. De La Timone
city: Nancy
country: France
facility: C.H.U. de Nancy - Hopital St Julien
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Chu Pitie-Salpetriere AP-HP
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bamberg
country: Germany
facility: Klinikum Bamberg
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: UniversitaetsKlinikum Heidelberg
city: Regensburg
country: Germany
facility: Universitaetskliniken Regensburg
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Milano
country: Italy
facility: Istituto Scientifico H.S. Raffaele
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni Battista Di Torino-Universita Di Torino
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum - Universiteit van Amsterdam
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Den Haag
country: Netherlands
facility: Medisch Centrum Haaglanden - Westeinde
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Maastricht
country: Netherlands
facility: Maastro Clinic - Maastricht Radiation Oncology
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Daniel den Hoed Cancer Center
city: Barcelona
country: Spain
facility: Hospital Clinic Universitari
city: Barcelona
country: Spain
facility: ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
city: Geneve
country: Switzerland
facility: Hopital Cantonal Universitaire De Geneve
city: Zurich
country: Switzerland
facility: Universitaetsspital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon And Exeter Hospital
city: Leeds
country: United Kingdom
facility: St. James'S University Hospital
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital campus
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
Study officials:
affiliation: Universitatsklinikum Heidelberg
name: Wolfgang Wick
role: STUDY_CHAIR
affiliation: Princess Margaret Hospital, Canada
name: Warren P. Mason, MD
role: STUDY_CHAIR
affiliation: The Cleveland Clinic
name: Michael A. Vogelbaum, MD, PhD
role: STUDY_CHAIR
affiliation: Medical Research Council
name: S. Erridge
role: STUDY_CHAIR
affiliation: Sir Charles Gairdner Hospital - Nedlands
name: Anna Nowak, MD
role: STUDY_CHAIR
References:
citation: Tesileanu CMS, Sanson M, Wick W, Brandes AA, Clement PM, Erridge SC, Vogelbaum MA, Nowak AK, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Rogers L, Taal W, Ruda R, Weller M, McBain C, van Linde ME, Aldape K, Jenkins RB, Kros JM, Wesseling P, von Deimling A, Hoogstrate Y, de Heer I, Atmodimedjo PN, Dubbink HJ, Brouwer RWW, van IJcken WFJ, Cheung KJ, Golfinopoulos V, Baumert BG, Gorlia T, French PJ, van den Bent MJ. Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial. Clin Cancer Res. 2022 Jun 13;28(12):2527-2535. doi: 10.1158/1078-0432.CCR-21-4283.
citation: van den Bent MJ, Tesileanu CMS, Wick W, Sanson M, Brandes AA, Clement PM, Erridge S, Vogelbaum MA, Nowak AK, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Rogers L, Taal W, Ruda R, Weller M, McBain C, Reijneveld J, Enting RH, Caparrotti F, Lesimple T, Clenton S, Gijtenbeek A, Lim E, Herrlinger U, Hau P, Dhermain F, de Heer I, Aldape K, Jenkins RB, Dubbink HJ, Kros JM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, French P, Baumert BG. Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2021 Jun;22(6):813-823. doi: 10.1016/S1470-2045(21)00090-5. Epub 2021 May 14.
citation: van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Ruda R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. doi: 10.1016/S0140-6736(17)31442-3. Epub 2017 Aug 8.