Bevacizumab Versus Bevacizumab Plus Vorinostat in Adults With Recurrent Glioblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Genentech
Merck Sharp and Dohme Corp.
Brain Tumor Trials Collaborative
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01266031
First received: December 22, 2010
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Brain Cancer
Drug: Vorinostat
Drug: Bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Adaptive Randomized Trial of Bevacizumab Versus Bevacizumab Plus Vorinostat in Adults With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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 . ] [ Designated as safety issue: No ]
    PFS is time measured in months to disease progression. Participants must at least 4 weeks after surgery to begin treatment in the adaptive randomized Phase 2 portion of the trial. PFS in participants in the surgical arm determined from the date of randomization to the treatment arms and not from the date of registration in the trial.

  • Maximum tolerated dose (MTD) [ Time Frame: Assessed with each 28 day cycle ] [ Designated as safety issue: Yes ]
    MTD defined as the dose level at which 1/6 patients experience dose limiting toxicity (DLT), and that MTD dose used for the Phase II part of the study.


Estimated Enrollment: 108
Study Start Date: July 2011
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat + Bevacizumab
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.
Drug: Vorinostat
Phase I: 400 mg by mouth once a day on days 1 to 7, and days 15 to 21 in a 28 day cycle.
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Drug: Bevacizumab
Phase I: 10 mg/kg by vein on day 1 and 15 of a 28 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Experimental: Bevacizumab MTD
Phase II Bevacizumab Alone
Drug: Bevacizumab
Phase II: 10 mg/kg/dose by vein on days 1 and 15 of a 28 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monocloal antibody
  • rhuMAB-VEGF
Experimental: Bevacizumab + Vorinostat
Phase II Bevacizumab + Vorinostat
Drug: Vorinostat
Phase II: 400 mg/day by mouth on days 1 to 7 and days 15 to 21 of a 28 day cycle.
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza

  Hide Detailed Description

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 </= 3 times upper limit normal and alkaline phosphatase </= 2 times upper limit normal, total bilirubin </= 1.5 mg/dl), "Patients with high bilirubin levels related to known diagnosis of benign hyperbilirubinemia (Gilbert's syndrome) will be eligible", and adequate renal function (BUN </= 1.5 times institutional normal and Creatinine < 1.5 mg/dl) prior to registration. These tests must be performed within 14 days prior to registration.
  11. Patients receiving treatment with any antiepileptic medications except valproic acid (because of its HDAC inhibitory activity) can be included in the study. Vorinostat is not metabolized by cytochrome P450 3A4 (CYP 3A4); however, vorinostat may potentially suppress CYP 3A4 activity. Therefore, patients should preferably be treated with non-enzyme inducing anti-epileptic medications although this is not mandatory. If enzyme-inducing antiepileptic drugs are used, monitoring of these drug levels should be considered, as considered clinically appropriate by the treating physician.
  12. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 14 days prior to registration. Women of childbearing potential must not be pregnant, must not be breast-feeding and must practice adequate contraception for the duration of the study, and for 30 days after the last dose of study medication. Patients must not be pregnant because animal studies show that bevacizumab and Vorinostat are teratogenic.
  13. Patient must be able to tolerate the procedures required in this study including periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.
  14. Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 12 weeks (84 days) from the completion of radiation therapy to study entry except if there is unequivocal evidence for tumor recurrence (such as histological confirmation or advanced imaging data such as PET scan) in which case at least 4 weeks (28 days) from completion of radiation therapy will suffice (Note: for patients who have undergone surgery to confirm recurrence after radiation therapy, guidelines in 4.9a should be followed).
  15. Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical/pathological documentation of disease.
  16. Male patients on treatment with Vorinostat must agree to use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication .

Exclusion Criteria:

  1. Inability to comply with protocol or study procedures (for example, an inability to swallow tablets).
  2. Prior treatment with bevacizumab or vorinostat.
  3. Patients receiving valproic acid (VPA), an anticonvulsant drug with HDAC inhibitor properties, will be excluded, unless they are switched to an alternative agent prior to treatment initiation. A 5-day wash out period is required. Patients who have failed prior treatment with other histone deacetylase inhibitors will be excluded.
  4. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent.
  5. Any condition, including the presence of clinically significant laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. These would include, a) Active infection (including persistent fever) including known AIDS or Hepatitis C infection, b) Diseases or conditions that obscure toxicity or dangerously alter drug metabolism, c) Serious intercurrent medical illness (e.g. symptomatic congestive heart failure).
  6. Current, recent (within 4 weeks (28 days) of the first infusion of this study), or planned participation in an experimental antitumor drug study(other than the current one).
  7. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix or bladder), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
  8. Inadequately controlled hypertension (defined as systolic blood pressure > 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 </= 1g of protein in 24 hours to be eligible).
  21. Known hypersensitivity to any component of bevacizumab
  22. 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..
  23. Patients with spinal disease (metastasis) and/or leptomeningeal disease will not be allowed in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01266031

Contacts
Contact: MD Anderson Cancer Center (713) 792-6600
Contact: Marta Penas-Prado, MD 713-792-2883

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Brain & Spine Center    713-792-6600      
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech
Merck Sharp and Dohme Corp.
Brain Tumor Trials Collaborative
Investigators
Principal Investigator: Marta Penas-Prado, MD UT MD Anderson Cancer Center
Study Chair: Vinay Puduvalli, MD Brain Tumor Trials Collaborative, and Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01266031     History of Changes
Other Study ID Numbers: BTTC11-02, BTTC11-02, 2010-0429, NCI-2011-00302
Study First Received: December 22, 2010
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Malignant glioma
Recurrent Glioblastoma
Glioblastoma multiforme
Gliosarcoma
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic oligoastrocytoma
Vorinostat
SAHA
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza
Bevacizumab
Avastin
Anti-VEGF monoclonal antibody
rhuMAb-VEGF

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antibodies
Antibodies, Monoclonal
Vorinostat
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014