Cancer types
  • Neuro-oncology
Title of study
IDH mutated 1p/19q intact lower grade glioma following resection: Wait Or Treat? IWOT – A phase III study
Version Number
Approval Date 
3.0, August 1, 2020
Short Title
I-WOT
Study site
Principle Investigator
M. van den Bent
Investigator Maastro
Dr. D. Eekers
Sponsor
EORTC
Trial registry

https://clinicaltrials.gov/ct2/show/NCT03763422NCT03763422

Objectives 

Determine whether early postoperative treatment results in a longer survival without further treatments and in the end a longer overall survival, and whether earlier treatment results in the earlier occurrence of delayed adverse effects of treatment.

Primary Endpoint 

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) ]

Secondary Endpoints 

1. 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 ]
2. 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 ]
3. 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 ]
4. 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.
5. 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.
6. 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.
7. 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.