Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients with Anaplastic Astrocytoma or Glioblastoma: A Phase Ib Study (STEAM)

Completed

Conditions: anaplastic astrocytoma IDHwt
glioblastoma
10029211

Registration Number: NL-OMON50615

Lead Sponsor: European Organisation for Research in Treatment of Cancer (EORTC)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

Specifics for groups A and B , - Newly diagnosed glioblastoma or anaplastic
astrocytoma, IDH1R132H-nonmutant by immunohistochemistry locally assessed, with
FFPE tissue available for central MGMT testing (treatment allocation will be
performed based on centrally assessed MGMT result)
- Tumor debulking surgery, including partial resection
- Age > 65 and considered non-eligible for combination therapy (TMZ/RT*TMZ) in
Investigator's opinion
- Brain MRI within 14 days before the first dose of TG02
- central assessment of MGMT promoter methylation , Specifics for group C , -
IDH1R132H-non-mutant glioblastoma or anaplastic astrocytoma at first relapse
with tissue available from first surgery
- Brain MRI at the time of progression or 14 days before the first dose of TG02
and availability of last brain MRI before progression diagnosis for upload to
the EORTC Imaging Platform for post-hoc central review of progression
- Diagnosis of recurrence more than 3 months after the end of RT for firstline
treatment
- Patient may have been operated for recurrence. If operated:
- surgery completed at least 2 weeks before initiation of TG02 and
patients should have fully recovered as assessed by investigator.
- a post-surgery MRI made within 72 hours; , - For non-operated
patients: recurrent disease must be at least one bidimensionally measurable
contrast-enhancing lesion with clearly defined margins by MRI scan, with
minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based
on a MRI scan done within 2 weeks prior to registration *
- Age * 18 years
- Intention to be treated with standard RT/TMZ*-- >TMZ for initial treatment
and at least one dose of TMZ administered; RT alone or chemotherapy alone as
initial treatment are not permitted, All groups
- Karnofsky Performance Score (KPS) of 60-100
- Recovered from effects of debulking surgery, postoperative infection and
other complications of surgery (if any) (CTCAE grade 0 and 1 acceptable)
- Adequate bone marrow, renal and hepatic function within the following ranges
within 7 days before the first dose of TG02:
* WBC * 3 x109/L
* ANC * 1.5x109/L
* Platelet count of * 100 x109/L independent of transfusion
* Hemoglobin * 10 g/dl or * 6.2 mmol/L
* Bilirubin * 1.5 × ULN
* ALT and AST * 2.5 × ULN
* Cockcroft*Gault calculated or measured creatinine clearance of * 30 mL/min
- Life expectancy > 8 weeks , - For men of reproductive potential and women of
childbearing potential: adequate contraception
- written informed consent
- Ability to take oral medication

Exclusion Criteria

REGISTRATION , Specifics for groups A and B , * prior radiotherapy with overlap
of radiation fields with the planned radiotherapy in this study (Group A)
* prior therapy for glioblastoma or anaplastic astrocytoma before surgery ,
Specifics for group C , * discontinuation of TMZ for toxicity during first-line
treatment
* no other treatment except surgery for the treatment of the first recurrence ,
All groups
* use of enzyme-inducing anti-epileptic drugs (EI-AED) within 7 days prior to
the first dose of TG02 ,
* history of ventricular arrhythmia or symptomatic conduction abnormality in
past 12 months prior to registration
* congestive heart failure (New York Heart Association Class III to IV,
symptomatic ischemia, uncontrolled by conventional intervention, or myocardial
infarction within 6 months prior to enrollment
* prolonged QTc interval (males: > 450 ms; females: > 470 ms)
* known contraindication to imaging tracer or any product of contrast media
* MRI contraindications , * concurrent severe or uncontrolled medical disease
, * known human immunodeficiency virus infection or acquired immune deficiency
syndrome , * previous other malignancies, except for any previous malignancy
which was treated with curative intent more than 3 years prior to enrollment,
and except for adequately controlled limited basal cell carcinoma of the skin,
squamous carcinoma of the skin or carcinoma in situ of the cervix , * Negative
serum or urine pregnancy test within 72 hours prior to the first dose for
WOCBP. Nursing must be discontinued at least 1 hour before first dose.
* Known hypersensitivity to the active substance of any of the excipients in
the TG02 formulation, dacabarzine and temozolomide, * 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>group A: determination of the maximum tolerated dose of TGO2 in combination<br /><br>with radiotherapy<br /><br>group B: determination of the maximum tolerated dose of TGO2 in combination<br /><br>with temozolomide<br /><br>Groep C: progression free survival at 6 months</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>voor alle groups: landmark and median overall and progression free survival;<br /><br>for group A and B quality of life, for group C neurological and clinical<br /><br>deterioration free survival, response rate and duration, the adverse event<br /><br>profile. Pharmacokinetics of TG02 (in group C only) at various timepoints</p><br>