Clinical trial NCT01564914: A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Glioblastoma Multiforme
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: The Cleveland Clinic
name: Case Comprehensive Cancer Center
First posted: 2012-03-28
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Median Overall Survival (OS)
timeFrame: 6 Months
Secondary outcomes:
measure: Median Duration That Patients Remained Progression Free on Study
timeFrame: Patients are scanned every 8 weeks for approximately 6 months
measure: Number of Participants With Adverse Events
timeFrame: Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months
measure: Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).
timeFrame: Patients are scanned every 8 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Tracon Pharmaceuticals Inc.
name: Charles Theuer, MD PhD
role: STUDY_DIRECTOR
References: