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 occurence of delayed adverse effects of treatment…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Next intervention free survival
Secondary outcome
Progression free survival
Overall survival
Neurological deterioration free survival
Time to deterioration of QOL
Time to deterioration of cognition
Seizure activity
Patient reported outcome
Safety profile (adverse events)
Correlation between molecular markers and outcome
In the active surveillance arm only: first intervention free survival
Background summary
This study aims at providing the evidence needed for the decision when to start
post-operative further adjuvant treatment of patients with a grade II or an
anaplastic astrocytoma, IDH mutant. These are relatively slow growing tumors
that cannot be cured, and that can remain asymptomatic of oligo-symptomatic for
a rather long period of time but at some point in time will become symptomatic.
Radiotherapy followed by chemotherapy prolongs survival in patients with these
tumors. but these treatment are also accompanied by side effects such as
fatigue and cognitive disturbances. It is unknown whether early dministration
of these treatments improve the overall treatment outcome and whether the
possibility of an earlier development of delayed side effects of early
treatment will be balanced by a survival increase. This question when to treat
is answered differently throughout the world, and has become acute again now
that improved survival of adding temozolomide chemotherapy to radiotherapy has
been demonstrated. It is also clear that earlier treatment may result in an
earlier occurence of delayed side effects of treatment, and those side effcts
may affect quality of survival. This study aims at providing the evidence
needed for patients and doctors to reach an informed decision when to start
postoperative treatment.
Study objective
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 occurence of delayed adverse
effects of treatment
Study design
Phase III study, patients are randomized to either immediate postoperative
treatment with radiotherapy and chemotherapy, or to a an active surveillance
study arm. In this arm patients are followed according to standard guidelines
every 6 months, and will undergo further treatment if tumor growth has been
documented according to the treating physicians discretion.
Intervention
The standard of care for these tumors, radiotherapy 50.4 of 59.4 Gy (depending
on the tumor grade) in fractions of 1.8 Gy,
followed by 12 cycles of temozolomide chemotherapy 150/200 mg/m2 day 1-5 every
4 weeks"
Study burden and risks
The burden for patients exists predominantly in the additional questionnaires
and the cognitive tests that are administered at baseline and basically every 6
months thereafter. The treatment of patients is according to standard of care
and brings no additional risks. Of note, there is lack of consensus at what
point in time resected patients should be treated further, and what criteria
should be used to guide this decision.
Av E Mounier 83/11
Brussel 1200
BE
Av E Mounier 83/11
Brussel 1200
BE
Listed location countries
Age
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;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003539-31-NL |
| ClinicalTrials.gov | NCT03763422 |
| CCMO | NL68939.078.19 |