NCT01648348|CompletedPhase 1Results

Bevacizumab With or Without Anti-Endoglin Monoclonal Antibody TRC105 in Treating Patients With Recurrent Glioblastoma Multiforme

Phase I/Comparative Randomized Phase II Trial of TRC105 Plus Bevacizumab Versus Bevacizumab in Bevacizumab-Naive Patients With Recurrent Glioblastoma Multiforme

National Cancer Institute (NCI)ClinicalTrials.gov

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6 other identifiers

NCI-2012-01989CDR0000737109N1174NCCTG-N1174U10CA180821U10CA025224

Study Type

interventional

Target

116

Locations

1 country

Sites

308

Timeline

RegisteredJul 2012

StartedNov 2012

CompletionApr 2017

Brief Summary

This partially randomized phase I/II trial studies the side effects and the best dose of anti-endoglin monoclonal antibody TRC105 when given together with bevacizumab and to see how well they work in treating patients with glioblastoma multiforme that has come back. Monoclonal antibodies, such as anti-endoglin monoclonal antibody TRC105 and bevacizumab, may find tumor cells and help kill them. Giving anti-endoglin monoclonal antibody TRC105 together with bevacizumab may be an effective treatment for glioblastoma multiforme.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

116

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Nov 2012

Longer than P75 for phase_1

Geographic Reach

1 country

308 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.5 years study duration

First Submitted

Initial submission to the registry

July 20, 2012

Completed

4 days until next milestone

First Posted

Study publicly available on registry

July 24, 2012

Completed

3 months until next milestone

Study Start

First participant enrolled

November 1, 2012

Completed

3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 11, 2016

Completed

11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 15, 2017

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

May 23, 2018

Completed

Last Updated

May 23, 2018

Status Verified

April 1, 2018

Enrollment Period

3.5 years

First QC Date

July 20, 2012

Results QC Date

September 21, 2017

Last Update Submit

April 24, 2018

Conditions

Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (2)

Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities
MTD for this study will be defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of DLT's will be reported here.
28 days
Progression-free Survival (PFS) (Phase II)
Progression Free Survival time is defined as the time from study randomization to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy or date last known to be alive, whichever is later. Patients who are still alive and have not progressed will be censored for progression at the time of the last tumor assessment. The time-to-progression distribution will be estimated using the Kaplan-Meier method.
The time from study randomization to documentation of disease progression, assessed up to 2 years

Secondary Outcomes (6)

Overall Toxicity Rate for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment (Phase II)
Up to 2 years
Overall Survival (Phase II)
The time from start of study therapy to death due to any cause, assessed up to 2 years
Progression Free Survival at 6 Months (PFS6) (Phase II) as Measured by the Percentage of Participants With Progression Free Survival at 6 Months
The time from study randomization to documentation of disease progression, assessed at 6 months
Quality of Life (QOL) as Assessed by the EORTC QLQ-C15-PAL Questionnaire [Item 15: Global Health Status/Quality of Life] (Phase II)
Baseline and 4 weeks
QOL Assessed by EORTC-QLQ-BN20 Patient Questionnaire [Items 1-20] (Phase II)
Baseline and 4 weeks
+1 more secondary outcomes

Other Outcomes (3)

Change in DCE-MRI Utility
Baseline to up to 2 years
Change in MRI ADC Utility
Baseline to up to 2 years
Changes in Tumor and Circulating Biomarkers
Baseline to up to 2 years

Study Arms (2)

Arm I (bevacizumab and TRC105)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105Biological: BevacizumabOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Quality-of-Life Assessment

Arm II (bevacizumab)

ACTIVE COMPARATOR

Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: BevacizumabOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Quality-of-Life Assessment

Interventions

Anti-Endoglin Chimeric Monoclonal Antibody TRC105BIOLOGICAL

Given IV

Also known as: TRC105

Arm I (bevacizumab and TRC105)

BevacizumabBIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar FKB238, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Arm I (bevacizumab and TRC105)Arm II (bevacizumab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (bevacizumab and TRC105)Arm II (bevacizumab)

Pharmacological StudyOTHER

Correlative studies

Arm I (bevacizumab and TRC105)Arm II (bevacizumab)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (bevacizumab and TRC105)Arm II (bevacizumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review (Phase I)
Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review; note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible; glioblastoma (GBM) with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q co-deleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q co-deletion status (Phase II)
Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
Measurable or evaluable disease by gadolinium MRI or contrast CT scan; note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
Absolute neutrophil count (ANC) \>= 1,500/mm\^3
Platelet count \>= 100,000/mm\^3
White blood cells (WBC) \>= 3,000/mL
Hemoglobin \>= 10.0 g/dL; note: this level may be reached by transfusion
Total bilirubin =\< institutional upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2 x ULN
Creatinine =\< ULN
Life expectancy \>= 12 weeks
Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
Urine protein creatinine (UPC) ratio \< 1; note: urine protein must be screened by urine analysis for UPC ratio; for UPC ratio \>= 1.0, 24-hour urine protein must be obtained and the level should be \< 1,000 mg for registration
+12 more criteria

You may not qualify if:

Any of the following:
Pregnant women
Nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for at least 6 months after treatment has ended
Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)
Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)
Prior hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (Phase I and II)
Prior hypersensitivity to triptan derivatives (Phase I and II)
Other active malignancy =\< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
Uncontrolled infection
Immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive and currently receiving combination antiretroviral therapy; patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
History of hypertensive crisis or hypertensive encephalopathy
Clinically significant cardiovascular disease defined as follows:
+17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (308)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Saint Jude Medical Center

Fullerton, California, 92835, United States

Location

Saint Joseph Hospital - Orange

Orange, California, 92868, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Greenwich Hospital

Greenwich, Connecticut, 06830, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Stamford Hospital/Bennett Cancer Center

Stamford, Connecticut, 06904, United States

Location

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Christiana Gynecologic Oncology LLC