Nab-sirolimus in Recurrent High Grade Glioma and Newly Diagnosed Glioblastoma
A Phase 2, Open-label Study of ABI-009 (Nab-Rapamycin) in Patients With Recurrent High-grade Glioma and Patients With Newly Diagnosed Glioblastoma
1 other identifier
interventional
62
1 country
3
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2018
Typical duration for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 5, 2018
CompletedFirst Posted
Study publicly available on registry
March 13, 2018
CompletedStudy Start
First participant enrolled
August 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 26, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 26, 2022
CompletedResults Posted
Study results publicly available
November 7, 2023
CompletedNovember 7, 2023
November 1, 2023
4.1 years
March 5, 2018
September 14, 2023
November 4, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
ORR
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.
Through study completion (up to 48 months)
Secondary Outcomes (4)
Median PFS
Through study completion (up to 48 months)
PFS Rate at 6 Months and 12 Months
6 and 12 months
OS
Through study completion (up to 48 months)
OS at 12 Months
12 months
Study Arms (6)
Arm A, Cohort 1: nab-sirolimus in patients with recurrent high grade glioma
EXPERIMENTALnab-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
EXPERIMENTALnab-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
EXPERIMENTALnab-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
EXPERIMENTALnab-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
EXPERIMENTALnab-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
EXPERIMENTALInduction 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)
Interventions
nab-sirolimus, single agent
temozolomide, combination
bevacizumab, combination
lomustine, combination
marizomib (MRZ), combination
temozolomide + radiotherapy, combination
Eligibility Criteria
You may qualify if:
- All subjects must have histologic evidence of high grade glioma (World Health Organization \[WHO\] grade 3 or grade 4) and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bi-dimensional product of enhancement, a new enhancing lesion, or a significant increase in T2 FLAIR). Subjects must have at least 1 measurable lesion by RANO criteria (≥ 10 mm in 2 perpendicular diameters).
- Patients must have previously failed a treatment regimen, including radiation and/or chemotherapy.
- No prior treatment with mTOR inhibitors.
- No prior treatment with temozolomide for the treatment of recurrent glioma for patients entering the ABI-009 + temozolomide cohort.
- No prior treatment with bevacizumab or any other anti-angiogenic agents, including sorafenib, sunitinib, axitinib, pazopanib, or cilengitide for the ABI-009 + bevacizumab arm.
- No prior treatment with lomustine for the ABI-009 + lomustine arm.
- No prior treatment with marizomib or any other proteasome inhibitors, including bortezomib, carfilzomib, or ixazomib, for patients entering the ABI-009 + marizomib cohort.
- At least 4 weeks from surgical resection and at least 12 weeks from the end of radiotherapy prior to enrollment in this study, unless relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if there are two MRIs confirming progressive disease that are approximately 4 weeks apart.
- Histologically confirmed newly diagnosed glioblastoma.
- Patients must have had surgery and can have either non-measurable disease or a measurable post-contrast lesion after surgery detected by MRI.
- No prior treatment with mTOR inhibitors, and no prior local or systemic therapy for GBM.
You may not qualify if:
- Co-medication or concomitant therapy that may interfere with study results, including anti-coagulants and enzyme-inducing anti-epileptic drugs (EIAEDs).
- History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months.
- Pregnant or breast feeding.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics \& psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state.
- Active gastrointestinal bleeding.
- Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥90 mm Hg.
- Patients with history of intestinal perforations, fistula, hemorrhages and/or hemoptysis ≤6 months prior to first study treatment.
- Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy.
- Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
- Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving the first dose of ABI-009.
- Known other previous/current malignancy requiring treatment within ≤ 3 years except for limited disease treated with curative intent, such as in situ prostate cancer, intracapsular renal cancer, cervical carcinoma in situ, squamous or basal cell skin carcinoma, and superficial bladder carcinoma.
- Any comorbid condition that restricts the use of study drug and confounds the ability to interpret data from the study as judged by the Investigator or Medical Monitor.
- Known Human Immunodeficiency Virus (HIV), or active Hepatitis B or Hepatitis C.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
St. Joseph Heritage Healthcare
Fullerton, California, 92835, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663, United States
John Wayne Cancer Institute
Santa Monica, California, 90404, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Aadi Medical Information
- Organization
- Aadi Bioscience, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2018
First Posted
March 13, 2018
Study Start
August 1, 2018
Primary Completion
August 26, 2022
Study Completion
August 26, 2022
Last Updated
November 7, 2023
Results First Posted
November 7, 2023
Record last verified: 2023-11