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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01564914
Recruitment Status : Completed
First Posted : March 28, 2012
Results First Posted : June 12, 2019
Last Update Posted : June 12, 2019
Sponsor:
Collaborators:
The Cleveland Clinic
Case Comprehensive Cancer Center
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.

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)

Condition or disease Intervention/treatment Phase
Glioblastoma Glioblastoma Multiforme Drug: TRC105 Drug: Bevacizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
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 Start Date : May 2012
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

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 Name: carotuximab

Drug: Bevacizumab
IV
Other Name: Avastin




Primary Outcome Measures :
  1. Median Overall Survival (OS) [ Time Frame: 6 Months ]
    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 :
  1. Median Duration That Patients Remained Progression Free on Study [ Time Frame: Patients are scanned every 8 weeks for approximately 6 months ]
    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.

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

  3. Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)). [ Time Frame: Patients are scanned every 8 weeks ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01564914


Locations
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United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
The Cleveland Clinic
Case Comprehensive Cancer Center
Investigators
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Study Director: Charles Theuer, MD PhD Tracon Pharmaceuticals Inc.
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Responsible Party: Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01564914    
Other Study ID Numbers: 105GM201/Case 1312
First Posted: March 28, 2012    Key Record Dates
Results First Posted: June 12, 2019
Last Update Posted: June 12, 2019
Last Verified: May 2019
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors