A Phase II/III Study of High-dose Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme

  • STATUS
    Recruiting
  • End date
    Jan 1, 2022
  • participants needed
    100
  • sponsor
    VU University Medical Center
Updated on 1 May 2021
platelet count
measurable disease
neutrophil count
EGFR
glioblastoma multiforme
temozolomide
recurrent glioblastoma
stereotactic radiosurgery
lomustine

Summary

In this study the investigators will evaluate the effect of high-dose, intermittent sunitinib versus treatment with lomustine in patients with recurrent glioblastoma multiforme. The investigators hypothesize that sunitinib, when given in a high-dose, intermittent schedule, will achieve adequate concentration levels in the tumor and will, besides its anti-angiogenic properties, inhibit gliomagenesis by inhibition of multiple kinases.

Description

Study design: Multicenter, phase II/III, randomized clinical trial with high-dose sunitinib versus lomustine (CCNU) in patients with recurrent GBM.

Hypothesis: Sunitinib, when given in a high-dose, intermittent schedule, may exhibit improved efficacy in patients with recurrent GBM with an acceptable toxicity profile, compared to lomustine.

Study population: Adult patients with recurrent GBM.

Primary objective:

  • To determine the effect of high-dose sunitinib versus lomustine on six-month progression-free survival (PFS6) in patients with recurrent GBM, using the RANO criteria.

Secondary objectives:

  • To determine the effect of high-dose sunitinib on overall survival (OS 9, OS 12) in patients with recurrent GBM.
  • To assess the objective radiological response rate, using the RANO criteria.
  • To assess toxicity, using the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.
  • To assess patient-oriented criteria: steroid use and health-related quality of life (reported by patients and caregivers/relatives).
  • To explore the potential value of blood markers for molecular diagnostics, disease and response monitoring.
  • To explore if MGMT promoter methylation status modulates the response to sunitinib.

Treatment: After randomization, 100 patients will be divided equally over two treatment groups and will receive:

  • Group 1 (experimental arm): Sunitinib, 700 mg administered orally every 2 weeks.
  • Group 2 (control arm): Lomustine 110 mg/m2, taken orally on day 1 every 6 weeks.

Disease will be assessed by MRI according to an uniform neuro-oncology protocol every 6 weeks for the first 6 months and every 12 weeks until documented progression. Safety profile of both treatment strategies will be assessed separately for each cycle of therapy and every 12 weeks after the end of treatment if adverse effects have not resolved or are newly emerging. Furthermore, quality of life assessment takes place every 6 weeks using questionnaires.

Details
Condition Glioblastoma Multiforme, Glomerular Basement Membrane, Malignant neoplasm of brain, Brain Tumor (Pediatric), Glioblastoma, Adult, Brain Cancer, Brain Tumor, Glioblastoma, Adult, Glioblastoma, Adult, recurrent brain tumors, glioblastoma, Glioblastoma, Adult, Glioblastoma, Adult, Glioblastoma, Adult
Treatment Sunitinib, Lomustine
Clinical Study IdentifierNCT03025893
SponsorVU University Medical Center
Last Modified on1 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Signed (by the patient or legally acceptable representative) and dated Informed Consent Form
Histologically confirmed de novo or secondary glioblastoma with unequivocal first progression, at least 3 months off radiotherapy
No more than one line of chemotherapy (concurrent and adjuvant temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization
Patients may have undergone surgery for recurrence. If operated, residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence
No radiotherapy, stereotactic radiosurgery or brachytherapy as treatment for recurrence
Patients must have a Karnofsky Performance Score 70%
Patients need to have adequate hematological, renal and hepatic function as assessed by the following laboratory requirements to be conducted within seven days prior to start study treatment
Hemoglobin 7.0 mmol/L
Absolute neutrophil count (ANC) 1.5 x 109/L
Platelet count 100 x 109/L
ALAT and ASAT 2.5 x ULN
Serum creatinine eGFR 50 ml/min
Albumin 25 g/L
Age 18 years

Exclusion Criteria

Evidence of a significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
Patients with a prior (< 5 years) or concomitant second malignancy
Prior radiotherapy in the abdomen or in the lungs or in more than 3 vertebrae in the spine (Less than 3 vertebrae are considered a small radiation field and eligibility will be decided on an individual basis from the PI)
Poorly controlled hypertension despite adequate blood pressure medication. Blood pressure must be 160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements
Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds.)
Initial MR-scan of the brain showing intratumoral hemorrhage, except for stable post-operative grade 1 hemorrhage
Known hypersensitivity to sunitinib or to its excipients
Presence of any significant central nervous system or psychiatric disorder(s) that would interfere with the patient's compliance
Use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes
Drug or alcohol abuse
Use of strong hepatic enzyme-inducing antiepileptic drugs, such as carbamazepine, phenobarbital and phenytoin. If a patient uses one or more of these specific antiepileptic drugs, they must switch to an antiepileptic drug that does not interact with cytochrome P450 (CYP450) liver enzymes, such as levetiracetam, prior to the start of study treatment
Females who are pregnant or breast-feeding
Any evidence of a disease or condition that might affect compliance with the protocol or interpretation of the study results or render the patient at high risk from treatment complications
Unwillingness or inability to comply with study and follow-up procedures
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
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