Phase 2
N=35
Oral Pazopanib Plus Oral Topotecan Metronomic Antiangiogenic Therapy for Recurrent Glioblastoma Multiforme (A) Without Prior Bevacizumab Exposure and (B) After Failing Prior Bevacizumab
Glioblastoma · Glioblastoma Multiforme · Gliosarcoma · Brain Neoplasms · Central Nervous System Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT01931098 ↗Enrolled (actual)
35
Serious AEs
25.7%
Results posted
Sep 2020
Primary outcome: Primary: Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment — 0.44; 0.18; 0.11; 0 proportion of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- topotecan (Drug); pazopanib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Sep 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment |
0.44; 0.18; 0.11; 0 | — |
| SECONDARY Overall Survival |
7.1; 6.3 | — |
| SECONDARY Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle |
1.1; 1.9; 2.3; 0.8; 3.5; 2.9 | — |
| SECONDARY Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle |
2.1; 3.6; 3.7; 1.4; 6.0; 4.2 | — |
| SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) |
9; 21 | — |
Summary
Background:
Glioblastoma is the most common and most aggressive type of malignant brain tumor. The drug pazopanib is used to treat people with a type of kidney cancer. Topotecan is used to treat lung cancer. Both topotecan and pazopanib have individually been used to treat patients with glioblastoma and some anti-tumor activity has been found. Researchers want to see if these two drugs together may be able to help people with glioblastoma.
Objectives:
To learn if pazopanib with topotecan can help control glioblastoma. Also, to study the safety of this drug combination.
Eligibility:
Adults at least 18 years old whose glioblastoma has returned after treatment.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Brain computed tomography (CT) or magnetic resonance imaging (MRI) For these, participants lay in a machine that takes pictures.
Chest CT scan or x-ray
Heart electrocardiogram (EKG)
A questionnaire about quality of life
Participants will be assigned to a study group.
Participants will take the study drugs for 28-day cycles for up to 1 year. They will take capsules of topotecan by mouth once every day. They will take tablets of pazopanib by mouth once every day.
Participants will write in a diary the times they take the study drugs.
Participants will have several study visits during each cycle. These may include
Blood pressure measurement
Blood and urine tests
EKG
Physical exam and/or neurological exam
Brain MRI or CT scan to check the status of the disease
A symptom questionnaire
At the end of treatment, participants will have a physical exam. They may have blood drawn.
Participants will have follow-up calls once every 3 months to check.
Eligibility Criteria
- General Inclusion Criteria
- Patients with histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM or GS is made. Patients must have evidence of progression of the GBM or GS on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Patient must have failed prior chemoradiation with temozolomide and any other therapies except BEV (group A), or must have failed primary chemoradiation and a BEV-incorporating treatment (group B).
- Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy). The intent therefore is that patients had no more than 3 prior therapies
(initial and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse.
For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse.
- Patients must be greater than 12 weeks following completion of chemoradiation or any additional radiation to reduce the chance of pseudoprogression.
- Measurable disease is required unless patient is post-operative and in that case patient can have no evidence of disease.
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
- Archived tumor tissue must be available for all subjects for confirmation of the diagnosis before or during treatment. Samples must be provided within 4 weeks of enrollment.
- Patients must be greater than or equal to 18 years old.
- Patients must have a Karnofsky performance status of greater than or equal to 60.
- At the time of registration: Patients must have recovered from the toxic effects of prior therapy: greater than or equal to 28 days from any investigational agent, greater than or equal to 28 days from prior cytotoxic therapy, greater than or equal to 14 days from vincristine, greater than or equal to 42 days from nitrosoureas, greater than or equal to 21 days from procarbazine administration, >21 days from bevacizumab administration and greater than or equal to 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of noncytotoxic agents should be directed to Academic Principal Investigator (PI).
- Patients must have adequate organ function:
- Bone marrow function (White blood cell (WBC) greater than or equal to 3,000/microl, absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, platelet count of greater than or equal to 100,000/mm^3, and hemoglobin greater than or equal to 10 gm/dl).
---Eligibility level for hemoglobin may be reached by transfusion.
- Liver function (alanine amino transferase (ALT) and aspartate aminotransferase (AST) 1.5 mg/dL, calculated creatinine clearance greater than or equal to 50 cc/min), and urine protein to creatinine ratio of 28 days from surgery.
- Residual disease following resection of recurrent GBM or GS 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, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
- Patients must have failed prior radiation therapy and must have an interval of greater than or equal to
Data sourced from ClinicalTrials.gov (NCT01931098). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.