Phase 2
Completed N=96
Phase I/II Adaptive Randomized Trial of Bevacizumab Versus Bevacizumab Plus Vorinostat in Adults With Recurrent Glioblastoma
Source: ClinicalTrials.gov NCT01266031 ↗Enrolled (actual)
96
Serious AEs
26.4%
Results posted
Sep 2016
Primary outcomePrimary: Progression Free Survival (PFS) at 6 Months — 0.29; 0.23 Months — p=0.26
Summary
The goal of this Phase I portion of this clinical research study is to find the highest tolerable dose of bevacizumab with or without vorinostat, that can be given to patients with malignant gliomas. The safety of these drug combinations will also be studied.
The goal of this Phase II part of this clinical research study is to learn if bevacizumab when given with or without vorinostat can help to control malignant gliomas. The safety of these drug combinations will also be studied.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) at 6 Months |
0.29; 0.23 | 0.26 |
| PRIMARY Maximum Tolerated Dose (MTD) of Oral Vorinostat Used With Bevacizumab |
400 | — |
| SECONDARY Time to Progression (TTP) |
4.07; 3.71; 0.59; 0.62; 0.29; 0.28 | — |
| SECONDARY Overall Survival (OS) |
9.24; 7.80 | — |
| SECONDARY Effects of Bevacizumab With and Without Vorinostat Upon Biomarkers of Angiogenesis Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PIGF), and Basic Fibroblast Growth Factor (bFGF) |
— | — |
| SECONDARY Effects of Bevacizumab With and Without Vorinostat Upon Biomarkers of Angiogenesis Stromal Cell-derived Factor α (SDF1α), and Angiopoietin 1 (Ang 1) and 2 (Ang 2) by Enzyme-linked Immunosorbent Assay (ELISA) |
— | — |
| SECONDARY Percentage of Patients Rating Their Symptoms to be 7 or Greater on a 0-10 Scale Using the Mean Severity of the MD Anderson Symptom Inventory-Brain Tumor Module (MDSAI-BT) Self Reporting Tool |
2; 0; 0; 0 | — |
| SECONDARY Mean Symptom Severity Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Self Reporting Tool |
1.6; 1.3; 1.9; 2.2 | — |
| SECONDARY Mean Symptom Interference at the Time of Clinical Evaluation |
2.2; 1.7; 2.9; 2.9 | — |
| SECONDARY Radiological Response |
— | — |
| SECONDARY Number of Participants With Serious and Non-Serious Adverse Events |
6; 38; 47 | — |
Eligibility Criteria
- INCLUSION CRITERIA:
Patients will be included in the study based on the following criteria.
- Patients must have histologically proven glioblastoma, gliosarcoma or anaplastic glioma to be eligible for the Phase I component of this protocol. Anaplastic gliomas include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant glioma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made. Only patients with histologically proven or imaging proven recurrent glioblastoma or gliosarcoma will be eligible for the Phase II component. Wafer acceptable if recurrence is confirmed.
- All patients must sign an informed consent indicating their awareness of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.
- Patients must be 18 years old or older.
- Patients must have a Karnofsky performance status (KPS) equal or greater than 60
- At the time of registration:
- Patients must have recovered from the toxic effects of prior therapy to 140 mmHg and/or diastolic blood pressure > 90 mmHg).
- Prior history of hypertensive encephalopathy.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- History of myocardial infarction or unstable angina within 6 months prior to Day 1.
- History of stroke or transient ischemic attack within 6 months prior to Day1.
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.
- History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study. Patients with recent resection will be eligible for entry into the surgical arm of the study but will follow guidelines as in section 4.9 .
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.
- Serious, non-healing wound, active ulcer, or untreated bone fracture.
- Proteinuria as demonstrated by:
- Urine protein: creatinine (UPC) ratio greater than or equal to 1.0 at screening OR
- Urine dipstick for proteinuria greater than or equal to 2+ (patients discovered to have greater than or equal to 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate less than or equal to 1g of protein in 24 hours to be eligible).
- Known hypersensitivity to any component of bevacizumab.
- Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential is required for study treatment.
Data sourced from ClinicalTrials.gov (NCT01266031). 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. Informational only — not medical advice.