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Glioblastoma MultiformePhase 2NCT00923117

Sunitinib to Treat Recurrent Brain Cancer

A Phase 2 study testing Sutent (sunitinib) in people with Glioblastoma Multiforme and Malignant Gliomas, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Background: One way tumors are able to grow is by forming new blood vessels that supply them with nutrients and oxygen. Sunitinib blocks certain proteins on the surface of tumor and blood vessel cells that are involved with the formation of new blood vessels. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sutent (sunitinib)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
1 siteUnited States
Study dates
Jun 2008to Jun 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant gliomas include glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
  • Patients may have received prior therapy with bevacizumab, but not within six weeks of starting treatment with sunitinib. Patients who received prior therapy with bevacizumab must have demonstrated radiographic disease progression while being treated with bevacizumab.
  • Patients must have progressed after radiation and temozolomide therapy and have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry. If the patient has had prior stereotactic radio surgery, true tumor progression must be corroborated by fludeoxyglucose 18F (FDG)-positron emission tomography (PET) or magnetic resonance (MR) spectroscopy imaging.
  • Patients must have evidence of tumor progression by contrast enhanced perfusion magnetic resonance imaging (MRI) or computed tomography (CT) scan. This scan should be performed within 14 days prior to registration and on a five-day stable dose of steroids. If the steroid dose is increased between the date of imaging and registration, a new baseline MR/CT is required. The same type of scan (i.e., MRI or CT) must be used throughout the period of protocol treatment for tumor measurement.
  • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
  • They have recovered from the effects of surgery.
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  • Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/MRI should be done:
  • no later than 96 hours in the immediate post-operative period, or
  • at least 4 weeks post-operatively, and
  • within 14 days of registration, and
  • on a steroid dosage that has been stable for at least 5 days.
  • Normal organ and marrow function defined as: total leukocyte count greater than or equal to 3000 cells/ul, absolute neutrophil count (ANC) greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times the upper limit of normal, and bilirubin less than or equal to 1.5 times the upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL , serum calcium less than or equal to 12.0 mg/dL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to 1.5 times the upper limit of normal, prothrombin time (PT) less than or equal to 1.5 upper limits of normal (ULN). Eligibility level for hemoglobin may be reached by transfusion.
  • The effects of sunitinib on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • All patients or their previously designated durable power of attorney (DPA) (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study.
  • Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks.
  • Patients must have a Karnofsky performance status of greater than or equal to 60.
  • Patients must have recovered from the toxic effects of prior therapy: 2 weeks from any investigational agent, two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine, 1 week for non-cytotoxic agents, (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.), and 4 weeks from other cytotoxic therapy. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
  • Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy.
  • This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Minorities will actively be recruited to participate.

Who cannot join

  • Patients who, in the view of the treating physician, have significant active cardiac, hepatic, renal, or psychiatric diseases are ineligible.
  • Patients with a history of prior therapy directed against vascular endothelial growth factor (VEGF) (e.g. sorafenib, pazopanib, Zactima (ZD6474), AZD2171), with the exception of bevacizumab, will not be allowed to enroll.
  • Concurrent use of other standard chemotherapeutics or investigative agents.
  • Patients known to have a malignancy (other than their malignant glioma) that has required treatment in the last 12 months and/or are expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix).
  • Patients who have an active infection.
  • Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 3 months after the completion of sunitinib therapy.
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  • Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatory agents, cyclooxygenase -2 (COX-2) inhibitors).
  • Serious or non-healing wound, ulcer or bone fracture
  • History of any of the following within 6 months of study entry: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, stroke, myocardial infarction or unstable angina. Patients will not undergo diagnostic screening for any of these conditions.
  • Invasive procedures defined as follows:
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
  • Anticipation of need for major surgical procedures during the course of the study
  • Core biopsy within 7 days prior to start of therapy
  • Uncontrolled hypertension (greater than 150/100 mmHg) while on antihypertensive medications.
  • New York Heart Association class II or greater congestive heart failure.
  • Serious cardiac arrhythmia requiring medication.
  • Evidence of bleeding diathesis, coagulopathy, or international normalized ratio (INR) greater than 1.5.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib.
  • Patients receiving any enzyme inducing anti-epileptic drugs (EIAEDs) and other potent cytochrome P450 3A4 (CYP3A4) modulators (per Appendixes B and C) within two weeks prior to treatment start are ineligible.
  • Baseline echocardiogram with ejection fraction less than 50% or greater than or equal to 20% decrease from a prior study
  • corrected QT interval(QTc) interval greater than 500 msec on baseline electrocardiogram (EKG).
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sunitinib.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase II Trial of Sunitinib in the Treatment of Recurrent Malignant Gliomas

Background:

One way tumors are able to grow is by forming new blood vessels that supply them with nutrients and oxygen.

Read more

Sunitinib blocks certain proteins on the surface of tumor and blood vessel cells that are involved with the formation of new blood vessels.

Blocking these proteins may prevent the tumor cells or blood vessels from continuing to grow.

Objectives:

To determine whether sunitinib can cause tumors to shrink or stabilize in patients with recurrent brain cancer.

Eligibility:

Patients 18 years of age or older with brain cancer whose disease has worsened after standard treatment with surgery, radiation.

Design:

Patients take a sunitinib pill once a day in 4-week treatment cycles. Treatment may continue as long as the tumor remains stable or decreases in size and the side effects of treatment are tolerated.

Routine blood tests are done every 2 weeks during the first 8 weeks of treatment and then every 4 weeks after that.

Magnetic resonance imaging (MRI) scans are done before starting treatment (at baseline) and at the end of every 4-week cycle to monitor tumor growth.

Positron emission tomography (PET) scans are done at baseline and at the end of the first cycle.

Neurological and physical examinations are done at baseline, at week 2 of treatment and at the end of every treatment cycle.

Health-related quality of life is assessed every 4 weeks.

Pregnancy tests, electrocardiograms and echocardiograms are repeated as needed.

Read the detailed description

Background:

Solid tumors have multiple mechanisms for stimulating angiogenesis with the vascular endothelial growth factor (VEGF)-kinase insert domain receptor (KDR) axis being only one of them. Sunitinib, through its multiple tyrosine kinase receptor targets, represents an attempt to capitalize on the concept of targeting multiple mechanisms responsible for glioma-associated angiogenesis. Sunitinib inhibits platelet derived growth factor receptor (PDGFR) and c-kit (stem cell factor (SCF) receptor) at nanomolar concentrations. The combination blocks all three known major glioma-mediated angiogenic mechanisms (VEGF, c-kit, PDGF). Based on this scientific rationale, the promising anti-glioma activity of sunitinib in preclinical models, and the promising clinical data in patients with gliomas treated with other VEGF inhibitors, we are now proposing a phase II trial of sunitinib in patients with recurrent malignant gliomas.

Objectives:

To evaluate the anti-glioma activity of sunitinib in patients with recurrent malignant gliomas who are either naive or resistant to prior bevacizumab therapy.

Eligibility:

Patients with recurrent malignant glioma are eligible for this study.

Design:

This is a phase II study with a target enrollment of 64 (32 with glioblastoma multiforme (GBM) and 32 with anaplastic glioma (AG)) patients who have not progressed on prior treatment with anti-VEGF therapy, and 64 (32 with GBM and 32 with AG)patients who have progressed on prior bevacizumab therapy.

Sunitinib will be self-administered orally at 37.5 mg daily, with dose adjustments allowed for toxicity and concomitant drug interactions.

The primary endpoint is six-month progression free survival for both arms of the study.

We performed an interim analysis (see below) and after consulting with the pharmaceutical company (Pfizer) we believe that ending the study is the most appropriate course of action to take.

In the original design of the trial, for the AG stratum, the agent will be considered effective if at least 14 patients have not progressed by 6 months. Now, we have observed one out 10 Bev-naïve who haven't progressed by 6 months. Then given one patient in the first 10 patients whose PFS >=6, the conditional probability of observing at least 14 out of 32 patients who are 6 month-PFS is only 43% even if the true 6 months-PFS is 55%. Since in the first 10 patients, we only observed one patient with PFS>=6 months, it is unlikely that the true 6 month-PFS is 55%. The conditional power would be close to zero, if the true 6 month-PFS close to 10% as observed so far. Based on the conditional probability, the chance of a positive study is small, and hence the trial should be considered stopped for futility.

For Bev-resistant patients, because in the first 12 patients none had PFS >= 6 months the conditional probability of declaring the agent being effective is even lower and equals 12%, if the true PFS at 6 months is 55%. Essentially there is little chance that the agent can be declared effective.

Being tested
Sutent (sunitinib)
Keywords
Glioblastoma, Chemotherapy, Anti-Angiogenesis, Radiation, Brain Tumor, Malignant Glioma, Glioblastoma Multiforme
Medical subject headings
Glioblastoma, Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sutent (sunitinib)Drug

    Oral dose 37.5 mg daily on a continuous 4 week cycle

Study groups in NCT00923117
Study groupRoleWhat they receive
Bevacizumab resistant patientsExperimentalPatients who had tumor progression while treated with bevacizumab.
Receives: Drug: Sutent (sunitinib)
Bevacizumab naive patientsExperimentalPatients with progressive tumor who have not been treated with bevacizumab.
Receives: Drug: Sutent (sunitinib)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6-month Progression-free Survival.

    Time between the start of treatment to progression. Progression is defined by the RANO(Response Assessment in Neuro-Oncology) criteria. Progression is defined by any of the following: 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.

    Measured: 6 months

Secondary outcomes (1)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: 7/2/08 -12/6/13

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2009 (estimated)
  2. Study startJun 2008
  3. Primary completionJun 2012
  4. Study completionJun 2012

Why it stopped: The study was terminated based on results of an interim analysis for futility.

Resources

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00923117
Sponsor's protocol ID
080168
Other IDs
08-C-0168
Status last verified
Jul 2014
First submitted
17 Jun 2009
Last updated
30 Sep 2015
Data monitoring committee
Yes

Publications

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

    PubMed 17237035

  • Prados MD, Schold SC Jr, Fine HA, Jaeckle K, Hochberg F, Mechtler L, Fetell MR, Phuphanich S, Feun L, Janus TJ, Ford K, Graney W. A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro Oncol. 2003 Apr;5(2):96-103. doi: 10.1093/neuonc/5.2.96.

    PubMed 12672281

  • Prados MD, Warnick RE, Mack EE, Chandler KL, Rabbitt J, Page M, Malec M. Intravenous carboplatin for recurrent gliomas. A dose-escalating phase II trial. Am J Clin Oncol. 1996 Dec;19(6):609-12. doi: 10.1097/00000421-199612000-00016.

    PubMed 8931682

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sutent (sunitinib) in people with Glioblastoma Multiforme and Malignant Gliomas, run by National Cancer Institute (NCI) at 1 site in United States.

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 19 inclusion and 22 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: stopped early, as of the sponsor's last update on 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month Progression-free Survival. (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00923117, which also lists 3 linked publications.

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 30 Sep 2015.

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