IDH mutated 1p/19q intact lower grade glioma following resection: Wait Or Treat? IWOT - A phase III study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 127

Inclusion Criteria

Histologically WHO grade II (diffuse) or III (anaplastic) astrocytoma, IDHmt
without 1p/19q co-deletion (local diagnosis)
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.
Time since diagnostic surgery or first resection <= 6 months
No need for immediate radiotherapy followed by chemotherapy
Functional deficits due to the resection is allowed
Patients for whom by local judgment an active surveillance policy is a
realistic management alternative
Adults >= 18years of age
WHO PS 0-2
Adequate hematological, renal, and hepatic function
Presence of at least one paraffin block from the initial diagnosis for
pathology review and translational research. If a representative FFPE block is
not available, the collection of optimally 36, minimally 24 x 5 µm, unstained
slides is required.
Ability to take oral medication
Written informed consent

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
Functional deficits due to the tumor
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
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
Not pregnant, agree to use adequate birth control measures, no breast feeding
Prior or second invasive malignancy, with some defined exceptions
Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule;

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Next intervention free survival</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Progression free survival<br /><br>Overall survival<br /><br>Neurological deterioration free survival<br /><br>Time to deterioration of QOL<br /><br>Time to deterioration of cognition<br /><br>Seizure activity<br /><br>Patient reported outcome<br /><br>Safety profile (adverse events)<br /><br>Correlation between molecular markers and outcome<br /><br><br /><br>In the active surveillance arm only: first intervention free survival</p><br>