Overview

This trial is active, not recruiting.

Condition brain cancer
Treatments vorinostat, bevacizumab
Phase phase 1/phase 2
Targets VEGF, HDAC
Sponsor M.D. Anderson Cancer Center
Collaborator Genentech, Inc.
Start date July 2011
End date July 2016
Trial size 108 participants
Trial identifier NCT01266031, 2010-0429, BTTC11-02, NCI-2011-00302

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Phase I Vorinostat orally days 1 - 7 and days 15 - 21 in combination with Bevacizumab fixed dose 10mg/kg IV on Days 1 + 15 of 28 day cycle.
vorinostat SAHA
Phase I: 400 mg by mouth once a day on days 1 to 7, and days 15 to 21 in a 28 day cycle.
bevacizumab Avastin
Phase I: 10 mg/kg by vein on day 1 and 15 of a 28 day cycle.
(Experimental)
Phase II Bevacizumab Alone
bevacizumab Avastin
Phase II: 10 mg/kg/dose by vein on days 1 and 15 of a 28 day cycle.
(Experimental)
Phase II Bevacizumab + Vorinostat
vorinostat SAHA
Phase II: 400 mg/day by mouth on days 1 to 7 and days 15 to 21 of a 28 day cycle.

Primary Outcomes

Measure
Progression Free Survival (PFS)
time frame: Baseline until disease progression or death due to any cause, assessed at least 4 weeks after surgery to begin treatment in the adaptive randomized portion of the trial every 8 weeks up to 28 days after last dose (follow-up .
Maximum tolerated dose (MTD)
time frame: Assessed with each 28 day cycle

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. 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. 2. Patients must have shown unequivocal evidence for tumor progression as determined by an MRI scan done prior to study entry which will be reviewed by the treating physician to confirm and document recurrence. Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis using the local institutional standards for such determination including advanced imaging or surgery. 3. For the phase II portion of the study, patients may have had treatment for no more than 2 prior relapses. There is no limit to the number of relapses for the phase I portion of the study provided the functional status and other eligibility criteria for enrollment are met. 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 4. 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. 5. The baseline on-study MRI should be performed within 14 days (+ 3 working days) prior to registration but before starting treatment and on a steroid dosage that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration (or at that time), a new baseline MRI is required. The same type of scan, i.e., MRI, must be used throughout the period of protocol treatment for tumor measurement. 6. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: a) At least 4 weeks(28 days) have elapsed from the date of surgery and the patients have recovered from the effects of surgery. b) Evaluable or measurable disease following resection of recurrent Malignant Glioma is not mandated for eligibility into the study. c) To best assess the extent of residual measurable disease post-operatively, a 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 is required on a stable steroid dosage for at least 5 days. 7. Patients must be 18 years old or older. 8. Patients must have a Karnofsky performance status (KPS) equal or greater than 60. 9. At the time of registration: (1) Patients must have recovered from the toxic effects of prior therapy to < grade 2 toxicity per CTC version 4 (except deep vein thrombosis): 28 days from any investigational agent; 4 weeks (28 days) from prior cytotoxic therapy; 2 weeks (14 days) from vincristine; 6 weeks (42 days) from nitrosoureas; 3 weeks (21 days) from procarbazine administration; >1 week (7 days) for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). (2) Patients who receive anticancer agents for non-therapeutic purposes unrelated to this study (such as presurgically for obtaining pharmacology data for the agent) will be eligible to enter the study provided they have recovered from the toxic effects of the agent if any. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair. 10. Patients must have adequate bone marrow function (ANC>/= 1,500/mm^3 and platelet count of >/= 100,000/mm^3), adequate liver function (SGPT 140 mmHg and/or diastolic blood pressure > 90 mmHg). 9. Prior history of hypertensive crisis or hypertensive encephalopathy. 10. New York Heart Association (NYHA) Grade II or greater congestive heart failure. 11. History of myocardial infarction or unstable angina within 6 months prior to Day 1. 12. History of stroke or transient ischemic attack within 6 months prior to Day 1 13. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1. 14. History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1. 15. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). 16. 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 the protocol" 17. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1. 18. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1. 19. Serious, non-healing wound, active ulcer, or untreated bone fracture. 20. Proteinuria as demonstrated by: (a) Urine protein:creatinine (UPC) ratio >/= 1.0 at screening OR (b) Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate

Additional Information

Official title Phase I/II Adaptive Randomized Trial of Bevacizumab Versus Bevacizumab Plus Vorinostat in Adults With Recurrent Glioblastoma
Principal investigator Marta Penas-Prado, MD
Description Phase I: The Study Drugs Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die. Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels. Study Drug Administration: If you are found to be eligible to take part in this study, you will be assigned to receive 1 of 2 dose levels of vorinostat based on when you join this study. Unless you have side effects, you will remain in the same dose level for the entire study. The first 3 participants will receive the lower dose level. The next 3 participants will receive a higher dose, if no intolerable side effects were seen. - On Days 1-7 and 15-21 of every 28-day cycle, you will take vorinostat by mouth 1 time a day. - In addition, no matter which dose level you are assigned to, you will receive bevacizumab by vein over 30-90 minutes on Days 1 and 15 of every cycle. Vorinostat capsules should be swallowed whole and should not be opened. If a capsule is damaged or broken, spills of powder from vorinostat capsules should be cleaned up carefully. If you come in contact with the powder, you should wash your hands thoroughly. If the spill is on a surface, the area must be washed at least 3 times with rubbing alcohol, followed by water. Vorinostat capsules should be stored at room temperature (59°-86°F [15°-30°C]) in a dry area. You should take vorinostat with food,but not a high fat meal. Study Visits: At Weeks 1 and 3 of Cycle 1, blood (about 1 teaspoon) will be drawn for routine tests. At Week 2 of Cycle 1: - Your blood pressure will be recorded. - Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot normally. - Urine will be collected to check kidney function. At Week 4 of Cycles 1-2 and then every other cycle after that (Cycles 4, 6, 8, and so on): - You will be asked about any drugs you may be taking and if you have had any side effects. - You will have a physical exam, including measurement of your vital signs. - You will have a neurological exam. - Your performance status will be recorded. - You will have a brain MRI and DCE-MRI scans to check the status of the disease. - Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot normally. - If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy test. - Urine will be collected to check kidney function. At Week 2 of Cycles 2 and beyond: - Your blood pressure will be recorded. - Blood (about 1 teaspoon) will be drawn for routine tests. At Week 4 of Cycles 3, 5, 7, and so on: - Your blood pressure will be measured. - Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot normally. - If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy test. - Urine will be collected to check kidney function. Length of Study: You may take the study drugs for up to 1 year. You may continue to receive the study drugs beyond 1 year if your doctor decides that it is in your best interest. You will be taken off study early if the disease gets worse or you have intolerable side effects. Your participation on this study will end once you complete the end-of-dosing visit and long-term follow-up. End-of-Dosing Visit: After you are no longer taking the study drugs, you will have an end-of-dosing visit. At this visit, the following tests and procedures will be performed: - You will have a physical exam, including measurement of your vital signs. - You will have a neurological exam. - Your performance status will be recorded. - Blood (about 2 teaspoons) will be drawn for routine tests. - You will have a brain MRI and DCE-MRI scans to check the status of the disease. - If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy test. Long-Term Follow-Up: After you are no longer taking part in the study, every 3 months after that, you may be called and asked how you are feeling. This phone call should take about 5-10 minutes. This is an investigational study. Bevacizumab is FDA approved and commercially available for treatment of some types of brain cancer. Vorinostat is FDA approved and commercially available for some types of lymphoma. The use of these drugs in this combination is investigational. Up to 108 participants will take part in this study. Up to 18 patients will be enrolled in the Phase 1 portion of this study. Up to 6 will be enrolled at MD Anderson. Phase II: The Study Drugs: Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die. Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. If you are on of the first 20 participants in the Phase 2 part of the study, you will be randomly assigned to a group. If you are enrolled after the first 20 participants, you will be more likely to be enrolled in the group that is showing better results. - If you are in Group 1, you will take bevacizumab. - If you are in Group 2, you will take bevacizumab and vorinostat. Study Drug Administration: If you are in Group 1: °On Days 1 and 15 of every 28-day cycle, you will receive bevacizumab by vein over 30-90 minutes. If you are in Group 2: - On Days 1-7 and 15-21 of every 28-day cycle, you will take vorinostat by mouth 1 time a day. - On Days 1 and 15 of every cycle, you will receive bevacizumab by vein over 30-90 minutes. Vorinostat capsules should be swallowed whole and should not be opened. If a capsule is damaged or broken, spills of powder from vorinostat capsules should be cleaned up carefully. If you come in contact with the powder, you should wash your hands thoroughly. If the spill is on a surface, the area must be washed at least 3 times with rubbing alcohol, followed by water. Vorinostat capsules should be stored at room temperature (59°-86°F [15°-30°C]) in a dry area. You should take vorinostat with food, but not a high fat meal. Study Visits: At Week 2 of Cycle 1: - Your blood pressure will be recorded. - Blood (about 3 teaspoons) will be drawn for routine tests. - Urine will be collected to check kidney function. At Week 4 of Cycles 1-2 and then every other cycle after that (Cycles 4, 6, 8, and so on): - You will be asked about any drugs you may be taking and if you have had any side effects. - You will have a physical exam, including measurement of your vital signs. - You will have a neurological exam. - Your performance status will be recorded. - Blood (about 3 teaspoons) will be drawn for routine tests. - If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy test. - Urine will be collected to check kidney function. At Week 2 of every cycle: - Your blood pressure will be recorded. - Blood (about 1 teaspoon) will be drawn for routine tests. At Week 4 of Cycles 3, 5, 7, and so on: - Your blood pressure will be measured. - Blood (about 3 teaspoons) will be drawn for routine tests. - If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy test. - Urine will be collected to check kidney function. At Week 4 of Cycles 2, and every other cycle after that (Cycles 4, 6, 8, and so on), you will have a brain MRI scan to check the status of the disease. In addition, if you are having surgery to remove a tumor that has come back before you receive the study drugs, leftover tumor tissue from the surgery will be used for biomarker testing. At any time during the study, extra tests may be performed if the doctor thinks they are needed for your safety. The study doctor will tell you more about any extra tests. Length of Study: You may take the study drug(s) for up to 1 year. You may continue to receive the study drug(s) beyond 1 year if your doctor decides that it is in your best interest. You will be taken off study early if the disease gets worse or you have intolerable side effects. Your participation on this study will end once you complete the end-of-dosing visit and long-term follow-up. End-of-Dosing Visit: After you are no longer taking the study drugs, you will have an end-of-dosing visit. At this visit, the following tests and procedures will be performed: - You will be asked about any drugs you may be taking and if you have had any side effects. - You will have a physical exam, including measurement of your vital signs. - You will have a neurological exam. - Your performance status will be recorded. - Blood (about 2 teaspoons) will be drawn for routine tests. - You will have a brain MRI scan to check the status of the disease. - If you are able to become pregnant, you will have a blood (about 1 teaspoon) pregnancy test. Long-Term Follow-Up: After you are no longer taking part in the study, every 3 months after that, you may be called and asked how you are feeling. This phone call should take about 5-10 minutes. This is an investigational study. Bevacizumab is FDA approved and commercially available for treatment of some types of brain cancer. Vorinostat is FDA approved and commercially available for some types of lymphoma. The use of these drugs in this combination is investigational. Up to 108 participants will take part in this study. Up to 90 patients will be enrolled in the Phase 2 portion of this study. Up to 20 will be enrolled at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.