Glioblastoma Multiforme Clinical Trial
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.
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT05023551 -
Study of DSP-0390 in Patients With Recurrent High-Grade Glioma
|
Early Phase 1 | |
Recruiting |
NCT06059690 -
Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells
|
Phase 1/Phase 2 | |
Recruiting |
NCT04116411 -
A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients
|
Phase 2 | |
Terminated |
NCT01902771 -
Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors
|
Phase 1 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Completed |
NCT02386826 -
INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme
|
Phase 1 | |
Completed |
NCT00038493 -
Temozolomide and SCH66336 for Recurrent Glioblastoma Multiforme
|
Phase 2 | |
Withdrawn |
NCT03980249 -
Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells
|
Early Phase 1 | |
Recruiting |
NCT01923922 -
CT Perfusion in the Prognostication of Cerebral High Grade Glioma
|
N/A | |
Completed |
NCT01956734 -
Virus DNX2401 and Temozolomide in Recurrent Glioblastoma
|
Phase 1 | |
Completed |
NCT01301430 -
Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.
|
Phase 1/Phase 2 | |
Completed |
NCT01402063 -
PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation
|
Phase 2 | |
Suspended |
NCT01386710 -
Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT00995007 -
A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas
|
Phase 2 | |
Terminated |
NCT01044966 -
A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma
|
Phase 1/Phase 2 | |
Terminated |
NCT00990496 -
A Study Using Allogenic-Cytomegalovirus (CMV) Specific Cells for Glioblastoma Multiforme (GBM)
|
Phase 1 | |
Completed |
NCT00402116 -
Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients
|
Phase 1/Phase 2 | |
Completed |
NCT00112502 -
Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
|
Phase 2 | |
Completed |
NCT00504660 -
6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients
|
Phase 2 | |
Recruiting |
NCT05366179 -
Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc
|
Phase 1 |