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

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ClinicalTrials.gov Identifier: NCT00626990
Recruitment Status : Active, not recruiting
First Posted : February 29, 2008
Last Update Posted : February 3, 2021
Sponsor:
Collaborators:
NCIC Clinical Trials Group
Radiation Therapy Oncology Group
Medical Research Council
Cooperative Trials Group for Neuro-Oncology
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE February 28, 2008
First Posted Date  ICMJE February 29, 2008
Last Update Posted Date February 3, 2021
Actual Study Start Date  ICMJE December 2007
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2016)
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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 28, 2008)
Overall survival as measured from the day of randomization
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2016)
  • Progression-free survival [ Time Frame: from randomization till the date of disease progression or death (assessed up to estimated 15 years from FPI) ]
  • Neurological deterioration-free survival [ Time Frame: from randomization till the date of neurological deterioration or death (assessed up to estimated 15 years from FPI) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2008)
  • Progression-free survival
  • Neurological deterioration-free survival
  • Quality of life as assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 and the Brain Cancer Module-20
  • Toxicity as measured by CTCAE version 3.0
  • Development of cognitive deterioration as measured by the Mini Mental Status Exam
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Trial of Anaplastic Glioma Without 1p/19q LOH
Official Title  ICMJE Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma. The CATNON Intergroup Trial.
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, 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: RT alone
    radiation therapy alone
    Interventions:
    • Genetic: DNA methylation analysis
    • Other: laboratory biomarker analysis
    • Procedure: quality-of-life assessment
    • Radiation: radiation therapy
  • Active Comparator: RT & Concurrent CT
    Radiotherapy and concurrent temozolomide chemotherapy
    Interventions:
    • Drug: temozolomide
    • Genetic: DNA methylation analysis
    • Other: laboratory biomarker analysis
    • Procedure: quality-of-life assessment
    • Radiation: radiation therapy
  • Active Comparator: RT + Adjuvant CT
    Radiotherapy plus adjuvant temozolomide chemotherapy
    Interventions:
    • Drug: temozolomide
    • Genetic: DNA methylation analysis
    • Other: laboratory biomarker analysis
    • Procedure: adjuvant therapy
    • Procedure: quality-of-life assessment
    • Radiation: radiation therapy
  • Active Comparator: RT & Concurrent CT + adjuvant CT
    Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy
    Interventions:
    • Drug: temozolomide
    • Genetic: DNA methylation analysis
    • Other: laboratory biomarker analysis
    • Procedure: adjuvant therapy
    • Procedure: quality-of-life assessment
    • Radiation: radiation therapy
Publications * 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, Rudà 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. Erratum in: Lancet. 2017 Oct 7;390(10103):1644.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 9, 2016)
751
Original Enrollment  ICMJE
 (submitted: February 28, 2008)
748
Estimated Study Completion Date  ICMJE January 2024
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00626990
Other Study ID Numbers  ICMJE EORTC-26053-22054
NCIC CTG CEC.1 ( Other Identifier: NCI-C )
RTOG-0834 ( Other Identifier: RTOG )
2006-001533-17 ( EudraCT Number )
P04839 ( Other Grant/Funding Number: Merck )
MRC BR14 ( Other Identifier: MRC CTU )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE
  • NCIC Clinical Trials Group
  • Radiation Therapy Oncology Group
  • Medical Research Council
  • Cooperative Trials Group for Neuro-Oncology
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
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
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP