Glioblastoma MultiformePhase 2/3STELLARNCT03025893
A Phase II/III Study of High-dose, Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme
A Phase 2/3 study testing Sunitinib and Lomustine in people with Glioblastoma Multiforme and Glioblastoma, Adult, run by Amsterdam UMC, location VUmc at 3 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Glioblastoma, Adult, Glioblastoma
- What is being tested?
- Sunitinib and Lomustine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesNetherlands
- Study dates
- 31 Aug 2018to 1 Jan 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- 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
Who cannot join
- 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.
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- 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.
- 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.
- Drug or alcohol abuse.
- 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.
Trial locations and contacts
3 sites in 1 country.
Jorien Janssen, MD contact
Netherlands3 sites, 3 recruiting
- Recruiting
VU University Medical Center
Amsterdam
Jorien Janssen, MD, jorien.janssen@radboudumc.nl
Myra E Van Linde, MD
- Recruiting
University Medical Center Groningen
Groningen
Jorien Janssen, MD
Annemiek ME Walenkamp, MD PhD
- Recruiting
Radboud UMC
Nijmegen
Jorien Janssen, MD
Chantal Driessen, MD, PhD
About this study
Official title: A Phase II/III Study of High-dose, Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme: the STELLAR Study
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.
Read the detailed 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.
- Being tested
- Sunitinib, Lomustine
- Keywords
- Sunitinib, Lomustine, High-dose, Intermittent
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent
Sunitinib, 300 mg administered orally in a weekly schedule.
LomustineDrug
Also called CCNU
Lomustine 110 mg/m2, taken orally on day 1 every 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | Patients in this experimental arm will receive sunitinib in a high-dose, intermittent schedule. Receives: Drug: Sunitinib |
| Lomustine | Active comparator | Patients in this control arm will receive lomustine, currently used as second-line treatment in the case of recurrence. Receives: Drug: Lomustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-month progression-free survival (PFS-6)
Measured: 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).
Secondary outcomes (6)
Overall survival (OS)
Measured: 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
Response will be assessed according to the RANO criteria.
Measured: 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).
Adverse events (AEs)
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.
Measured: 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).
Health-related quality of life (HRQoL)
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.
Measured: HRQoL assessments will be performed at baseline and every 6 weeks until documented progression, assessed up to 36 months (End of Study).
Blood markers (TEP: tumor educated platelets, and miRNA)
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.
Measured: 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).
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.
Measured: At the end of the study (after 36 months), the treatment outcomes of all patients will be correlated with the MGMT promoter methylation status.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2017 (estimated)
- Study start31 Aug 2018
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.E. van Linde, Amsterdam UMC, location VUmc
- Investigators
- Myra E Van Linde, MD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03025893
- Sponsor's protocol ID
- 2016.221
- Acronym
- STELLAR
- Status last verified
- Apr 2021
- First submitted
- 9 Jan 2017
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Study of High-dose, Intermittent Sunitinib in Patients With Recurrent Glioblastoma Multiforme: the STELLAR Study
- ClinicalTrials.gov ID
- NCT03025893
- Acronym / sponsor ID
- STELLAR / 2016.221
- Keywords
- Sunitinib, Lomustine, High-dose, Intermittent
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 31 Aug 2018 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 20 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: SunitinibPatients in this experimental arm will receive sunitinib in a high-dose, intermittent schedule. |
| Lomustine | Active comparator | Drug: LomustinePatients in this control arm will receive lomustine, currently used as second-line treatment in the case of recurrence. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SunitinibAlso: SutentSunitinib, 300 mg administered orally in a weekly schedule. | Drug | Sunitinib |
| LomustineAlso: CCNULomustine 110 mg/m2, taken orally on day 1 every 6 weeks. | Drug | Lomustine |
Primary outcome
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).
6 secondary outcomes
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).
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).
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).
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).
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorien Janssen, MD contact
Myra E Van Linde, MD principal investigator
Amsterdam UMC, location VUmc
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sunitinib and Lomustine in people with Glioblastoma Multiforme and Glioblastoma, Adult, run by Amsterdam UMC, location VUmc at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Myra E Van Linde, MD (+31 20 444 4321, trialoffice-onc@vumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021.