ANG1005 in Patients With Recurrent High-Grade Glioma

Study Overview
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Brief Summary
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This is a Phase 2 study to see if an investigational drug, ANG1005, can shrink tumor cells in patients with high-grade glioma. Another purpose of this study is to assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of ANG1005 in patients.

Detailed Description
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See above.

Official Title
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A Phase II, Open-Label, Multi-Center Study of ANG1005 in Patients With Recurrent High-Grade Glioma

Conditions
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Glioma, Glioblastoma, Brain Tumor, Recurrent

Intervention / Treatment
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* Drug: ANG1005
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old GBM and GBM variants, WHO Grade III anaplastic glioma diagnosis confirmed Radiologically confirmed recurrent and bi-dimensionally measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria Neurologically stable For bevacizumab-refractory patients, radiologic demonstration of tumor progression during bevacizumab therapy Karnofsky performance status (KPS) ≥ 80 Expected survival of at least 3 months Exclusion Criteria: More than three relapses Previous ANG1005/GRN1005 treatment Radiotherapy within 3 months. Therapy with bevacizumab within 4 weeks prior to Day 1 of treatment for recurrent WHO grade III anaplastic glioma patients (Arm 3) Evidence of significant intracranial hemorrhage Previous taxane treatment Prior therapy with bevacizumab for bevacizumab-naïve patients (Arm 1) NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 Grade ≥ 2 neuropathy Inadequate bone marrow reserve Any evidence of severe or uncontrolled diseases Participants with the presence of an infection including abscess or fistulae, or known infection with hepatitis C or B or HIV Known severe hypersensitivity or allergy to paclitaxel or any of its components

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>ANG1005 administered to bevacizumab-naive recurrent GBM participants | Drug: ANG1005<br>* ANG1005 at a starting dose of 650 mg/m^2 or 600 mg/m^2 by intravenous infusion once every 3 weeks<br>* Other names: GRN1005;|
| Experimental: Arm 2<br>ANG1005, with or without bevacizumab, administered to bevacizumab-refractory recurrent GBM participants | Drug: ANG1005<br>* ANG1005 at a starting dose of 650 mg/m^2 or 600 mg/m^2 by intravenous infusion once every 3 weeks<br>* Other names: GRN1005;Drug: Bevacizumab<br>* For participants enrolled in the bevacizumab-refractory recurrent GBM arm (Arm 2), treatments with bevacizumab may be continued and administered every 2 or 3 weeks at the Investigator's discretion.<br>* Other names: Avastin;|
| Experimental: Arm 3<br>ANG1005 administered to recurrent WHO Grade III anaplastic glioma participants | Drug: ANG1005<br>* ANG1005 at a starting dose of 650 mg/m^2 or 600 mg/m^2 by intravenous infusion once every 3 weeks<br>* Other names: GRN1005;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) (Arms 1 and 3) | To determine the radiologic ORR in bevacizumab-naïve recurrent Glioblastoma multiforme (GBM) patients (Arm 1)and in recurrent anaplastic glioma World Health Organization (WHO) Grade III patients (Arm 3) | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| PFS3 (Arm 2) | To determine the progression-free survival at 3 months (PFS3) in bevacizumab-refractory recurrent GBM patients (Arm 2) | Upon enrollment through end of study period (1 year after last patient is enrolled) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR in Arm 2 | To determine the ORR in Arm 2 | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| PFS at 3, 6 and 12 months | To determine the number of patients without progression at 3, 6 and 12 months in Arms 1 and 3 To determine the number of patients without progression at 6 and 12 months in Arm 2 | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Median PFS | To determine the median progression-free survival in each arm | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Duration of response | To determine the median duration of response in each arm | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Overall survival | To determine the median overall survival in each arm | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Safety and tolerability | To determine the number of participants with adverse events | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Plasma Pharmacokinetics of ANG1005 (Half-life [T1/2], Maximum Concentration [Cmax], Area Under the Curve [AUC]) | To determine the drug concentration and distribution in the blood (plasma) | At 0 h (pre-dose), at the end of infusion, at 2 and 4 hours post-dose on Day 1 of treatment cycles 1 and 3 (Week 1 and Week 9) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioma, glioblastoma, brain cancer, brain tumor, recurrent