A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma (105GM201)

A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab for the Treatment Of Recurrent or Progressive Glioblastoma That Has Progressed on Bevacizumab

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)

Study Overview

• Status: Completed
• Conditions: Glioblastoma; Glioblastoma Multiforme
• Intervention / Treatment: Drug: TRC105; Drug: Bevacizumab

Detailed Description

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
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRC105, Bevacizumab; Single arm study	Drug: TRC105; 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle; Other Names: carotuximab; Drug: Bevacizumab; IV; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Patients are scanned every 8 weeks

Collaborators and Investigators

• Sponsor: Tracon Pharmaceuticals Inc.
• Collaborators: The Cleveland Clinic; Case Comprehensive Cancer Center
• Investigators: Study Director: Charles Theuer, MD PhD, Tracon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 26, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (Estimate): March 28, 2012

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: May 21, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 105GM201/Case 1312