ABI-009 (Nab-rapamycin) in Recurrent High Grade Glioma and Newly Diagnosed Glioblastoma

• ClinicalTrials.gov Identifier: NCT03463265
• Recruitment Status: Active, not recruiting
• First Posted: March 13, 2018
• Last Update Posted: June 14, 2022
• Sponsor: Aadi Bioscience, Inc.
• Information provided by (Responsible Party): Aadi Bioscience, Inc.

Study Description

Brief Summary:

A phase 2, open-label study of ABI-009 (nab-Rapamycin) in patients with recurrent high grade glioma following prior therapy and subjects with newly diagnosed glioblastoma. ABI-009 will be tested as single agent or in combination with standard therapies.

Condition or disease	Intervention/treatment	Phase
High Grade Recurrent Glioma and Newly Diagnosed Glioblastoma	Drug: ABI-009; Drug: Bevacizumab; Drug: Temozolomide; Drug: Lomustine; Radiation: Radiation; Drug: Marizomib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Study of ABI-009 (Nab-Rapamycin) in Patients With Recurrent High-grade Glioma and Patients With Newly Diagnosed Glioblastoma
• Actual Study Start Date: August 1, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: ABI-009	Drug: ABI-009; ABI-009 as single agent or in combination with other agents; Other Name: nab-rapamycin, nanoparticle albumin-bound rapamycin
Experimental: ABI-009 + bevacizumab	Drug: ABI-009; ABI-009 as single agent or in combination with other agents; Other Name: nab-rapamycin, nanoparticle albumin-bound rapamycin; Drug: Bevacizumab; bevacizumab
Experimental: ABI-009 + temozolomide	Drug: ABI-009; ABI-009 as single agent or in combination with other agents; Other Name: nab-rapamycin, nanoparticle albumin-bound rapamycin; Drug: Temozolomide; temozolomide
Experimental: ABI-009 + lomustine	Drug: ABI-009; ABI-009 as single agent or in combination with other agents; Other Name: nab-rapamycin, nanoparticle albumin-bound rapamycin; Drug: Lomustine; lomustine
Experimental: ABI-009 + temozolomide + radiotherapy	Drug: ABI-009; ABI-009 as single agent or in combination with other agents; Other Name: nab-rapamycin, nanoparticle albumin-bound rapamycin; Drug: Temozolomide; temozolomide; Radiation: Radiation; radiation
Experimental: ABI-009 + marizomib	Drug: ABI-009; ABI-009 as single agent or in combination with other agents; Other Name: nab-rapamycin, nanoparticle albumin-bound rapamycin; Drug: Marizomib; marizomib

Outcome Measures

Primary Outcome Measures :

1. objective overall response rate according to RANO 2010 criteria [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 12 months ]
2. progression free survival [ Time Frame: 12 months ]
3. overall survival [ Time Frame: 12 months ]

Eligibility Criteria

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

Criteria

Inclusion Criteria Specific for Arm A

1. 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).
2. Patients must have previously failed a treatment regimen, including radiation and/or chemotherapy.
3. No prior treatment with mTOR inhibitors.
4. No prior treatment with temozolomide for the treatment of recurrent glioma for patients entering the ABI-009 + temozolomide cohort.
5. No prior treatment with bevacizumab or any other anti-angiogenic agents, including sorafenib, sunitinib, axitinib, pazopanib, or cilengitide for the ABI-009 + bevacizumab arm.
6. No prior treatment with lomustine for the ABI-009 + lomustine arm.
7. No prior treatment with marizomib or any other proteasome inhibitors, including bortezomib, carfilzomib, or ixazomib, for patients entering the ABI-009 + marizomib cohort.
8. 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.

Inclusion Criteria Specific for Arm B

1. Histologically confirmed newly diagnosed glioblastoma.
2. Patients must have had surgery and can have either non-measurable disease or a measurable post-contrast lesion after surgery detected by MRI.
3. No prior treatment with mTOR inhibitors, and no prior local or systemic therapy for GBM.

Exclusion Criteria Common for Both Arms A and B

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

1. Co-medication or concomitant therapy that may interfere with study results, including anti-coagulants and enzyme-inducing anti-epileptic drugs (EIAEDs).
2. History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months.
3. Pregnant or breast feeding.
4. 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.
5. Active gastrointestinal bleeding.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥90 mm Hg.
7. Patients with history of intestinal perforations, fistula, hemorrhages and/or hemoptysis ≤6 months prior to first study treatment.
8. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.
9. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
10. 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.
11. 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.
12. 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.
13. Known Human Immunodeficiency Virus (HIV), or active Hepatitis B or Hepatitis C.

Contacts and Locations

Locations

United States, California

St. Joseph Heritage Healthcare

Fullerton, California, United States, 92835

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

John Wayne Cancer Institute

Santa Monica, California, United States, 90404

Sponsors and Collaborators

Aadi Bioscience, Inc.

More Information

• Responsible Party: Aadi Bioscience, Inc.
• ClinicalTrials.gov Identifier: NCT03463265
• Other Study ID Numbers: GBM007
• First Posted: March 13, 2018
• Last Update Posted: June 14, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Glioblastoma; Glioma; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Sirolimus; Bevacizumab; Temozolomide; Lomustine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors