Nab-sirolimus in Recurrent High Grade Glioma and Newly Diagnosed Glioblastoma
- Conditions
- High Grade Recurrent Glioma and Newly Diagnosed Glioblastoma
- Interventions
- Drug: nab-sirolimusDrug: nab-sirolimus + bevacizumab
- Registration Number
- NCT03463265
- Lead Sponsor
- Aadi Bioscience, Inc.
- Brief Summary
Phase 2, open-label study of nab-sirolimus in patients with recurrent high grade glioma following prior therapy and patients with newly diagnosed glioblastoma. nab-Sirolimus was administered as single agent or in combination therapies.
- Detailed Description
A phase 2, open-label study of nab-sirolimus (also known as ABI-009, nab-rapamycin, albumin-bound rapamycin) in patients with recurrent high grade glioma following prior therapy and patients with newly diagnosed glioblastoma. nab-Sirolimus was administered as single agent or in combination therapies, including temozolomide, bevacizumab, lomustine, and marizomib.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm A, Cohort 1: nab-sirolimus in patients with recurrent high grade glioma nab-sirolimus nab-Sirolimus (ABI-009, nab-rapamycin, albumin-bound rapamycin) was administered at 100 mg/m2 as a 30-minute IV infusion on Days 1 and 8 of every 21-day cycle. Arm A, Cohort 2: nab-sirolimus + temozolomide (TMZ) in patients with recurrent high grade glioma nab-sirolimus + temozolomide nab-Sirolimus (60 mg/m 2 as a 30-minute IV infusion on Days 1, 8, and 15 of every 28-day cycle). Temozolomide (PO at 50 mg/m2 daily) Arm A, Cohort 3: nab-sirolimus + bevacizumab in patients with recurrent high grade glioma nab-sirolimus + bevacizumab nab-Sirolimus (IV 60 mg/m 2 as a 30-minute infusion on Days 1, 8, and 15 of every 28-day cycle). Bevacizumab (IV at a fixed dose of 5 mg/kg on Days 1 and 15 of every 28-day cycle). Arm A, Cohort 4: nab-sirolimus + lomustine (CCNU) in patients with recurrent high grade glioma nab-sirolimus + lomustine nab-Sirolimus was administered at 60 mg/m 2 as a 30-minute IV infusion on Days 1 and 8 of every 21-day cycle. CCNU was administered PO at 90 mg/m2 on Day 1 of each odd 21-day cycle (ie, every 6 weeks). Arm A, Cohort 5: nab-sirolimus + marizomib (MRZ) in patients with recurrent high grade glioma nab-sirolimus + marizomib (MRZ) nab-Sirolimus was administered at 60 mg/m 2 as a 30-minute IV infusion on Days 1, 8, and 15 of every 28-day cycle. MRZ was administered at 0.8 mg/m 2 as a 10-minute IV infusion on Days 1, 8, and 15 of every 28-day cycle. MRZ was administered approximately 10 minutes after the end of the nab-sirolimus infusion. Arm B: nab-sirolimus + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma nab-sirolimus + temozolomide + radiotherapy Induction Treatment (4 weeks) with nab-sirolimus (60 mg/m2 IV weekly); followed by Concomitant Treatment (standard of care; 2 cycles): nab-sirolimus (60 mg/m2 IV on Days 8 and 15 of every 21-day cycle) in combination with TMZ (75 mg/m2 PO daily for 6 weeks) + radiotherapy (30 × 200 cGy, 5 days/week); followed by Adjuvant Treatment (6 cycles) starting 4 weeks after Concomitant Treatment, with nab-sirolimus(60 mg/m2 IV on Days 1, 8, and 15 of every 28-day cycle) in combination with TMZ (150 mg/m2 PO daily on Days 1-5 of every 28-day cycle)
- Primary Outcome Measures
Name Time Method ORR Through study completion (up to 48 months) Objective overall response rate (ORR, according to Response Assessment in Neuro-Oncology \[RANO\]) by investigator-assessed radiologic review and defined as the proportion of patients who achieved a confirmed partial response (PR) or confirmed complete response (CR) per RANO 2010 criteria. PR is defined as greater than or equal to 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks.
- Secondary Outcome Measures
Name Time Method Median PFS Through study completion (up to 48 months) Progression-free Survival defined as number of months from the date of the first dose of study drug to the first observation of a disease progression or death due to any cause.
Progression is assessed according to Response Assessment in Neuro-Oncology (RANO) 2010 criteria based on MRI imaging, and includes ≥25% increase in the sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids.PFS Rate at 6 Months and 12 Months 6 and 12 months Progression-free survival rate at 6 months and 12 months was calculated as the proportion of patients who were progression-free and alive at 6 and 12 months, respectively.
Progression is assessed according to Response Assessment in Neuro-Oncology (RANO) 2010 criteria based on MRI imaging, and includes ≥25% increase in the sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids.OS Through study completion (up to 48 months) Median Overall Survival
OS at 12 Months 12 months Overall Survival rate at 12 months
Trial Locations
- Locations (3)
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
St. Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
John Wayne Cancer Institute
🇺🇸Santa Monica, California, United States