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Trial in Low Grade Glioma Patients: Wait or Treat (IWOT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03763422
Recruitment Status : Terminated (Poorly recruiting)
First Posted : December 4, 2018
Last Update Posted : February 1, 2022
Sponsor:
Collaborator:
Cooperative Trials Group for Neuro-Oncology (COGNO)
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE November 13, 2018
First Posted Date  ICMJE December 4, 2018
Last Update Posted Date February 1, 2022
Actual Study Start Date  ICMJE March 16, 2020
Actual Primary Completion Date December 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2018)
Next intervention free survival (FIFS) [ Time Frame: From the date of randomization until initiation of second treatment or death whichever occurs first assessed up to 11.5 years as of first patient in (FPI) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2018)
  • First intervention free survival (FIFS) [ Time Frame: from the date of randomization until initiation of preferably RT/TMZ or any other first therapeutic intervention (second surgery, RT, chemotherapy) or death (any cause) whichever occurs first assessed up to 11.5 years as of first patient in ]
  • Progression Free Survival (PFS) [ Time Frame: From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first assessed up to 11.5 years as of first patient in ]
  • Overall Survival [ Time Frame: From the date of randomization up to the date of death up to 1 year after first progression or start of second treatment in early treatment arm or first treatment in active surveillance arm assessed up to 11.5 years as of first patient in ]
  • Seizure activity [ Time Frame: The IWOT Seizure Control Composite Score Index can be completed up to 4 weeks before or after the planned assessment. A time window of 8 weeks is therefore available for each assessment. Assessed up to 11.5 years after FPI ]
    Seizure activity will be evaluated by the IWOT Seizure Control Composite Score Index completed by patients with an additional answer from the local investigator.
  • Safety profile: CTCAE [ Time Frame: The collection period will start from randomization and up to start of second treatment for patients in the early treatment arm and from randomization to first treatment, for patients in active surveillance arm. Assessed up to 11.5 years after FPI ]
    This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, for adverse event reporting. Hematological toxicity will be assessed on the basis of blood counts. The nadir count will be assessed for each cycle of TMZ therapy, and graded according to CTCAE. Non-hematological acute side effects will be assessed and reported separately for each cycle of TMZ therapy, and graded according to the Common Terminology Criteria for Adverse Events version 5.0.
  • Translational research [ Time Frame: tissue and blood at randomization and new tissue at repeated surgical interventions if patient consented for translational research.Assessed up to 11.5 years after FPI ]
    The main objectives of TR are the assessment of markers that can identify patients in whom an active surveillance policy is not recommended or who are at risk to develop delayed complications is important. Furthermore, identification of predictive factors that could guide when to start RT and chemotherapy would aid the implementation of an active surveillance approach in clinical practice.
  • HRQoL related to seizures [ Time Frame: From randomization until progression assessed up to 11.5 years as of FPI ]
    A seizure specific questionnaire will be used. The Seizure Control Composite Score Index is self-reported 7-item questionnaire developed to assess seizures frequency and severity.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial in Low Grade Glioma Patients: Wait or Treat
Official Title  ICMJE IDH Mutated 1p/19q Intact Lower Grade Glioma Following Resection: Wait Or Treat? IWOT - a Phase III Study
Brief Summary The 1635-EORTC-BTG study - Wait or Treat - concerns patients that represent a clinically favorable group of patients with IDHmutated astrocytoma (oligo-symptomatic), without a need for immediate post-operative treatment. It will establish whether early adjuvant treatment with radiotherapy and adjuvant temozolomide in resected IDHmutated astrocytoma will improve outcome, and whether benefits of early treatment outweigh potential side-effects of that, such as deterioration in neurocognitive function or Quality of Live, seizure activity and Patient Reported outcome compared to active surveillance.
Detailed Description Not Provided
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
  • Low-grade Glioma
  • Temozolomide
  • Phase III
  • Wait or Treat
Intervention  ICMJE
  • Drug: Temozolomide
    Oral Administration of Temozolomide
    Other Name: TMZ
  • Radiation: Radiotherapy
    50.4 Gy in 28 fractions over 6 weeks
    Other Name: RT
  • Procedure: Surgery
    Surgery
Study Arms  ICMJE
  • Experimental: Early Treatment arm
    Radiotherapy + Temozolomide
    Interventions:
    • Drug: Temozolomide
    • Radiation: Radiotherapy
  • Active Comparator: Active surveillance arm
    Treatment as per local practice
    Interventions:
    • Drug: Temozolomide
    • Radiation: Radiotherapy
    • Procedure: Surgery
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: December 2, 2021)
19
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2018)
624
Actual Study Completion Date  ICMJE December 29, 2021
Actual Primary Completion Date December 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically WHO grade II (diffuse) or III (anaplastic) astrocytoma, IDHmt without 1p/19q co-deletion (local diagnosis)
  • Time since diagnostic surgery or first resection ≤ 6 months
  • No need for immediate radiotherapy followed by chemotherapy
  • Having seizures only, without functional deficits due to the tumor (but the presence of functional deficits due to the resection is allowed)
  • Patients for whom by local judgment an active surveillance policy is a realistic management alternative
  • The patient is at least 18 years of age on day of signing informed consent
  • WHO PS 0-2
  • Adequate hematological, renal, and hepatic function, as follows:

    • Absolute neutrophil count ≥ 1.5 x 10*9/L
    • Platelets ≥ 100 × 10*9/L
    • Serum creatinine ≤ 1.5 times upper limit of laboratory normal (ULN)
    • Total serum bilirubin ≤ 1.5 × ULN
    • AST and ALT ≤ 2.5 × ULN
    • Alkaline phosphatase of ≤ 2.5 × ULN
  • Presence of at least one paraffin block from the initial diagnosis for pathology review and translational research. If a representative formalin-fixed, paraffin-embedded (FFPE) block is not available, the collection of optimally 36, minimally 24 x 5 µm, unstained slides is required.
  • At the time of randomization presence only of a non-enhancing tumor on T1 weighted contrast enhanced MR images; some faint non-nodular enhancement or enhancement that can be ascribed to the surgical resection or peri-operative ischemia is allowed. Preoperative enhancement is allowed provided this area is resected as shown on postoperative imaging
  • Ability to take oral medication
  • Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test done within 72 hours prior to randomization
  • Patients of childbearing / reproductive potential must agree to use adequate birth control measures, as defined by the investigator, during RT and TMZ treatment and for at least 6 months after the last TMZ cycle. A highly effective method of birth control is defined as those which result in low failure rate (i.e., less than 1 percent per year) when used consistently and correctly
  • Women who are breast feeding must agree to discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment
  • Male patients should be advised not to father a child and not to donate sperm up to 6 months after receiving the last dose of TMZ, and to seek advice on cryoconservation of sperm prior to treatment start
  • Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments
  • Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria:

  • Presence of signs of increased intracranial pressure after surgery
  • Requirement of steroids for control of tumor symptoms
  • Presence of uncontrolled seizures after surgery, defined as having both:

    • persistent seizures interfering with everyday life activities AND
    • failed three lines of anti-epileptic drug regimen, including at least one combination regimen
  • Presence of contra-indications for radiotherapy
  • Hypersensitivity to dacarbazine (DTIC), to the active substance or to any of the excipients used for TMZ capsules
  • Prior chemotherapy, or prior radiotherapy to the brain
  • Pregnancy or breastfeeding
  • Known HIV, chronic hepatitis B, or hepatitis C infection
  • Inability to take oral medication (e.g., frequent vomiting, partial bowel obstruction)
  • Concurrent severe or uncontrolled medical disease (e.g., active systemic infection, diabetes, hypertension, coronary artery disease, psychiatric disorder) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study
  • Prior or second invasive malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with PSA of less than or equal to 0.1 ng/mL). Other cancers for which the subject has completed potentially curative treatment more than 3 years prior to study entry are allowed
  • Presence 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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,   Austria,   Belgium,   Denmark,   France,   Italy,   Netherlands,   Spain,   Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03763422
Other Study ID Numbers  ICMJE EORTC-BTG-1635
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Cooperative Trials Group for Neuro-Oncology (COGNO)
Investigators  ICMJE
Principal Investigator: Martin Van den Bent EORTC Study Coordinator
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date January 2022

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