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

Sponsor

Aadi Bioscience, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03463265

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

18.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Aug 1, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: nab-rapamycin, nanoparticle albumin-bound rapamycin Drug: Marizomib marizomib

Outcome Measures

Primary Outcome Measures

objective overall response rate according to RANO 2010 criteria [12 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria Specific for Arm A

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.

Inclusion Criteria Specific for Arm B

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.

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:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph Heritage Healthcare	Fullerton	California	United States	92835
2	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
3	John Wayne Cancer Institute	Santa Monica	California	United States	90404