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

Primary Purpose

Glioblastoma, Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TRC105
Bevacizumab
Sponsored by
Tracon Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Cincinnati
  • University Hospitals of Cleveland
  • Cleveland Clinic
  • Ohio State University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TRC105, Bevacizumab

Arm Description

Single arm study

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Number of Participants With Adverse Events
Adverse event frequency per patient according to CTCAE version 4.0.
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.

Full Information

First Posted
March 26, 2012
Last Updated
May 21, 2019
Sponsor
Tracon Pharmaceuticals Inc.
Collaborators
The Cleveland Clinic, Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01564914
Brief Title
A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma
Acronym
105GM201
Official Title
A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab for the Treatment Of Recurrent or Progressive Glioblastoma That Has Progressed on Bevacizumab
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tracon Pharmaceuticals Inc.
Collaborators
The Cleveland Clinic, Case Comprehensive Cancer Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Glioblastoma Multiforme

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
A total of 6 initial patients were treated with 10 mg/kg of TRC105 monotherapy. All patients progressed within 2 months of initiating treatment, reflecting the rapid progression. Due to the lack of activity in this disease setting with TRC105 alone, the study was amended to treat patients with 10 mg/kg TRC105 weekly in combination with 10 mg/kg bevacizumab every two weeks.
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TRC105, Bevacizumab
Arm Type
Experimental
Arm Description
Single arm study
Intervention Type
Drug
Intervention Name(s)
TRC105
Other Intervention Name(s)
carotuximab
Intervention Description
10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
IV
Primary Outcome Measure Information:
Title
Median Overall Survival (OS)
Description
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 Outcome Measure Information:
Title
Median Duration That Patients Remained Progression Free on Study
Description
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
Title
Number of Participants With Adverse Events
Description
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
Title
Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).
Description
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.
Time Frame
Patients are scanned every 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histologically confirmed glioblastoma, recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy. Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma. Patients with up to 3 prior recurrences are allowed. Karnofsky performance status ≥ 70%. Age ≥ 18 years old. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Theuer, MD PhD
Organizational Affiliation
Tracon Pharmaceuticals Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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