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High Grade Recurrent Glioma and Newly Diagnosed GlioblastomaPhase 2NCT03463265

Nab-sirolimus in Recurrent High Grade Glioma and Newly Diagnosed Glioblastoma

A Phase 2 study testing nab-sirolimus, nab-sirolimus + temozolomide and nab-sirolimus + bevacizumab in people with High Grade Recurrent Glioma and Newly Diagnosed Glioblastoma, run by Aadi Bioscience, Inc. at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
nab-sirolimus, nab-sirolimus + temozolomide and nab-sirolimus + bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
3 sitesUnited States
Study dates
1 Aug 2018to 26 Aug 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • St. Joseph Heritage Healthcare

    Fullerton, California, 92835

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • John Wayne Cancer Institute

    Santa Monica, California, 90404

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
nab-sirolimus, nab-sirolimus + temozolomide, nab-sirolimus + bevacizumab, nab-sirolimus + lomustine, nab-sirolimus + marizomib (MRZ)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nab-sirolimusDrug

    nab-sirolimus, single agent

  • nab-sirolimus + temozolomideDrug

    Also called nab-sirolimus, temozolomide

    temozolomide, combination

  • nab-sirolimus + bevacizumabDrug

    Also called nab-sirolimus, bevacizumab

    bevacizumab, combination

  • nab-sirolimus + lomustineDrug

    Also called nab-sirolimus, lomustine (CCNU)

    lomustine, combination

  • nab-sirolimus + marizomib (MRZ)Drug

    Also called nab-sirolimus, marizomib (MRZ)

    marizomib (MRZ), combination

  • nab-sirolimus + temozolomide + radiotherapyDrug

    Also called nab-sirolimus, temozolomide, radiation

    temozolomide + radiotherapy, combination

Study groups in NCT03463265
Study groupRoleWhat they receive
Arm A, Cohort 1: nab-sirolimus in patients with recurrent high grade gliomaExperimentalnab-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.
Receives: Drug: nab-sirolimus
Arm A, Cohort 2: nab-sirolimus + temozolomide (TMZ) in patients with recurrent high grade gliomaExperimentalnab-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)
Receives: Drug: nab-sirolimus + temozolomide
Arm A, Cohort 3: nab-sirolimus + bevacizumab in patients with recurrent high grade gliomaExperimentalnab-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).
Receives: Drug: nab-sirolimus + bevacizumab
Arm A, Cohort 4: nab-sirolimus + lomustine (CCNU) in patients with recurrent high grade gliomaExperimentalnab-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).
Receives: Drug: nab-sirolimus + lomustine
Arm A, Cohort 5: nab-sirolimus + marizomib (MRZ) in patients with recurrent high grade gliomaExperimentalnab-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.
Receives: Drug: nab-sirolimus + marizomib (MRZ)
Arm B: nab-sirolimus + temozolomide + radiotherapy in patients with newly diagnosed glioblastomaExperimentalInduction 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)
Receives: Drug: nab-sirolimus + temozolomide + radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Through study completion (up to 48 months)

Secondary outcomes (4)

  1. Median PFS

    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.

    Measured: Through study completion (up to 48 months)

  2. PFS Rate at 6 Months 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.

    Measured: 6 and 12 months

  3. OS

    Median Overall Survival

    Measured: Through study completion (up to 48 months)

  4. OS at 12 Months

    Overall Survival rate at 12 months

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2018
  2. Study start1 Aug 2018
  3. Primary completion26 Aug 2022
  4. Study completion26 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03463265
Sponsor's protocol ID
GBM-007
Status last verified
Nov 2023
First submitted
5 Mar 2018
Last updated
7 Nov 2023
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing nab-sirolimus, nab-sirolimus + temozolomide and nab-sirolimus + bevacizumab in people with High Grade Recurrent Glioma and Newly Diagnosed Glioblastoma, run by Aadi Bioscience, Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR (time frame: Through study completion (up to 48 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03463265.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.

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