A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma

Tracon Pharmaceuticals Inc.22 enrolled

Overview

The purpose of this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy)

Angiogenesis plays a central role in the progression of solid cancer. TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on proliferating endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models. TRC105 has been well tolerated in patients with glioblastoma (GBM) as a single agent. The combination of TRC105 in combination with bevacizumab has demonstrated activity in bevacizumab refractory cancer patients. We hypothesize that TRC105 when administered with bevacizumab will have activity in GBM patients who progress on bevacizumab. By targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibition by bevacizumab, which could represent a major advance in GBM therapy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma Glioblastoma Multiforme

Interventions

TRC105DRUG

10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle

BevacizumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients with histologically confirmed glioblastoma, recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy. 2. Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma. 3. Patients with up to 3 prior recurrences are allowed. 4. Karnofsky performance status ≥ 70%. 5. Age ≥ 18 years old. 6. Normal organ function Exclusion Criteria: * Patients who have had previous treatment with TRC105. * Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury * Patients with cirrhosis, or active viral or nonviral hepatitis. * Patients with active bleeding or pathologic conditions that carry a high risk of bleeding,(i.e. hereditary hemorrhagic telangiectasia). * Patients who are currently receiving anticoagulation treatment * Patients unwilling or unable to comply with the protocol

Locations (4)

University of Cincinnati

Cincinnati, Ohio, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Outcomes

Primary Outcomes

Median Overall Survival (OS)

Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial

Time frame: 6 Months

Secondary Outcomes

Median Duration That Patients Remained Progression Free on Study

The median number of months that patients remained progression free was calculated using modified RANO criteria to determine progression. Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.

Time frame: Patients are scanned every 8 weeks for approximately 6 months

Number of Participants With Adverse Events

Adverse event frequency per patient according to CTCAE version 4.0.

Time frame: Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months

Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).

Number of patients who respond to study treatment according to modified RANO criteria was calculated (Objective Response Rate (ORR)). Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.

Data from ClinicalTrials.gov

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