Bevacizumab Beyond Progression (BBP)

NCT01740258 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00038098
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Studies which have separately studied bevacizumab for recurrent gliomas and bevacizumab for newly-diagnosed glioma have shown good results and the regimens have been well-tolerated by patients. This study seeks to investigate the use of bevacizumab with the standard therapy (radiation therapy and temozolomide) in newly diagnosed patients, followed by bevacizumab and temozolomide with the continuation of bevacizumab following progression. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis.

Conditions

Malignant Glioma; Grade 4 Malignant Glioma; Glioblastoma; Gliosarcoma

Keywords

malignant glioma; Grade 4 malignant glioma; glioblastoma; gliosarcoma; adult brain tumor

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  To assess the effect on overall survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of first diagnosis of grade IV malignant glioma.

  5 Years

Secondary Outcomes (2)

• Toxicity: Percentage of Subjects With Unacceptable Toxicities

  5 Years

• Progression-free Survival (PFS)

  5 Years

Study Arms (1)

Bevaczimab, Radiation Therapy, Temozolomide

EXPERIMENTAL

In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician.

Radiation: Radiation Therapy; Drug: Temozolomide; Drug: Bevacizumab

Interventions

Radiation Therapy RADIATION

Also known as: XRT

Bevaczimab, Radiation Therapy, Temozolomide

Temozolomide DRUG

Also known as: temo, temodar

Bevaczimab, Radiation Therapy, Temozolomide

Bevacizumab DRUG

Also known as: Avastin

Bevaczimab, Radiation Therapy, Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed WHO Grade IV primary malignant glioma (glioblastoma or gliosarcoma);
• Patients ≥ 18 years of age;
• An interval of at least 2 weeks, but not ≥ 8 weeks between prior surgical procedure and initiation of treatment;
• Karnofsky Performance Status (KPS) ≥ 60%
• Laboratory Values:
• Platelet Count ≥ 125,000 cells/µL
• Absolute neutrophil count (ANC) ≥ 1,500 cells/µL
• Adequate renal function indicated by all of the following:
• Serum creatinine ≤ 1.25 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 ml/min
• Urine dipstick for proteinuria \< 2+ unless a 24-hour urine protein \< 1 g of protein is demonstrated
• internationalized normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x upper limit of normal (ULN) within 7 days prior to first study treatment for patients not receiving anti-coagulation. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the first study treatment.
• Patients will sign an Institutional Review Board-approved informed consent form.
• Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as \< 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, \[i.e. with a failure rate of \< 1% per year\] are implants, injectables, combined oral contraceptives, intra-uterine device \[Intrauterine Device (IUD); only hormonal\], sexual abstinence or vasectomized partner) during the trial and for a period of \> 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 7 days prior to first study treatment.
• Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control \[i.e. with a failure rate of \< 1% per year\] include a female partner using implants, injectables, combined oral contraceptives, Intrauterine Device (IUDs) \[only hormonal\], sexual abstinence or prior vasectomy) during the trial and for a period of \> 6 months following the last administration of trial drugs.

You may not qualify if:

• Any prior treatment for any grade glioma, including, but not limited to gliadel wafers, immunotherapy (including vaccine therapy), radiation therapy or chemotherapy, irrespective of grade of the tumor (NOTE: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.);
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
• Active infection requiring intravenous antibiotics;
• Prior or current treatment with bevacizumab or other anti-angiogenic treatment (i.e. anti-vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) therapies or tyrosine kinase inhibitors) for any condition;
• Treatment with any other investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment;
• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
• Evidence of \> Grade 1 central nervous system (CNS) hemorrhage on post-operative MRI scan, unless repeat MRI or CT performed prior to initiating bevacizumab shows stable grade 1 or resolving (\< grade 1) CNS hemorrhage.
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) within 28 days of first study treatment;
• Prior history of hypertensive crisis, hypertensive encephalopathy, reverse posterior leukoencephalopathy syndrome (RPLS);
• Prior history of gastrointestinal perforation or abscess;
• Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment;
• History or evidence upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment;
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism \> NCI common toxicity criteria adverse event (CTCAE) Grade 3;
• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month of first study treatment;
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation);

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Links

• Preston Robert Tisch Brain Tumor Center at Duke
• Duke Cancer Institute
• Duke Cancer Center - Patient Care

MeSH Terms

Conditions

Glioma; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Radiotherapy; Temozolomide; norambreinolide-18,6alpha-olide; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Annick Desjardins, MD, FRCPC
• Organization: Duke University

annick.desjardins@duke.edu

919-681-1691

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2012
• First Posted: December 4, 2012
• Study Start: January 1, 2013
• Primary Completion: November 14, 2019
• Study Completion: November 14, 2019
• Last Updated: January 26, 2021
• Results First Posted: December 2, 2020

Record last verified: 2021-01

Locations

US (1)