A Phase II/III Study of High-dose, Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme (STELLAR)
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|ClinicalTrials.gov Identifier: NCT03025893|
Recruitment Status : Recruiting
First Posted : January 20, 2017
Last Update Posted : September 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme Glioblastoma, Adult Glioblastoma Recurrent Brain Tumor GBM||Drug: Sunitinib Drug: Lomustine||Phase 2 Phase 3|
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.
- 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.
- 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, 300 mg administered orally in a weekly schedule.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II/III Study of High-dose, Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme: the STELLAR Study|
|Actual Study Start Date :||August 31, 2018|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2020|
Patients in this experimental arm will receive sunitinib in a high-dose, intermittent schedule.
Sunitinib, 300 mg administered orally in a weekly schedule.
Other Name: Sutent
Active Comparator: Lomustine
Patients in this control arm will receive lomustine, currently used as second-line treatment in the case of recurrence.
Lomustine 110 mg/m2, taken orally on day 1 every 6 weeks.
Other Name: CCNU
- Six-month progression-free survival (PFS-6) [ Time Frame: From the date of randomization up to the date of first progression or death (any cause) whichever comes first, assessed up to 36 months (End of Study). ]
- Overall survival (OS) [ Time Frame: From the date of randomization up to the date of death, assessed up to 36 months. If study medication is discontinued for any reason, survival follow-up takes place every 12 weeks, also assessed up to 36 months (End of Study). ]
- Objective radiological response rate [ Time Frame: Disease will be assessed by MRI every 6 weeks for the first 6 months and every 12 weeks until documented progression, assessed up to 36 months (End of Study). ]Response will be assessed according to the RANO criteria.
- Adverse events (AEs) [ Time Frame: AEs will be monitored at every visit during study treatment or after discontinuation of study treatment in the case adverse events have not subsided, assessed up to 36 months (End of Study). ]At the end of the study, after 36 months, the number of participants with adverse events that are related to both treatments will be assessed and compared.
- Health-related quality of life (HRQoL) [ Time Frame: HRQoL assessments will be performed at baseline and every 6 weeks until documented progression, assessed up to 36 months (End of Study). ]Steroid use will be documented at every treatment cycle as an objective parameter for HRQoL. Furthermore, HRQoL will also be measured via EORTC questionnaires, which will be filled in by the participants every 6 weeks BEFORE their MRI.
- Blood markers (TEP: tumor educated platelets, and miRNA) [ Time Frame: Blood samples for RNA profiling will be drawn simultaneously with regular blood samples on five specific time points during study treatment and will be assessed after 36 months (End of Study). ]The five specific time points during study treatment are: (1) at baseline; (2) at the first outpatient visit; (3) after two weeks of treatment; (4) at the first response evaluation (first MRI); and (5) at the time of progression.
- MGMT promoter methylation status [ Time Frame: At the end of the study (after 36 months), the treatment outcomes of all patients will be correlated with the MGMT promoter methylation status. ]Previously obtained resection or biopsy material from the first-line treatment of these participants will be requested at the time of inclusion and used to determine the MGMT methylation status. After the End of Study (after 36 months) the MGMT promoter methylation status will be correlated with the response to treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03025893
|Contact: Henk MW Verheul, MD PhD||+31 20 444 firstname.lastname@example.org|
|Contact: Cyrillo G Brahm, MD||+31 20 444 email@example.com|
|VU University Medical Center||Recruiting|
|Contact: Cyrillo G Brahm, MD +31 20 444 4321|
|Principal Investigator: Henk WM Verheul, MD PhD|
|Sub-Investigator: Cyrillo G Brahm, MD|
|University Medical Center Groningen||Not yet recruiting|
|Contact: Cyrillo G Brahm, MD PhD|
|Principal Investigator: Annemiek ME Walenkamp, MD PhD|
|Sub-Investigator: Cyrillo G Brahm, MD|
|Principal Investigator:||Henk MW Verheul, MD PhD||VU University Medical Center|