Atezolizumab and Cabozantinib for the Treatment of Recurrent Glioblastoma

NCT05039281 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2021-0041NCI-2021-09119
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests the safety and side effects of atezolizumab in combination with cabozantinib and whether they work to shrink tumors in patients with glioblastoma that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help control the disease in patients with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma; Recurrent Gliosarcoma

Outcome Measures

Primary Outcomes (3)

• Progression-free survival (PFS)

  Will estimate the 6 months PFS distribution using the Kaplan-Meier method.

  At 6 momths

• Objective response rate

  Will be estimated with exact binomial 95% confidence intervals. Logistic regression will be used to explore the correlations between response rates and correlative markers.

  Up to 3 years

• Incidence of adverse events

  Will be estimated with exact binomial 95% confidence intervals. Adverse events will be tabulated by grade and by their relationship to the treatment.

  Up to 3 years

Study Arms (1)

Treatment (atezolizumab, cabozantinib)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on day 1 and cabozantinib PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Atezolizumab; Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Given PO

Treatment (atezolizumab, cabozantinib)

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (atezolizumab, cabozantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF)
• Ability and willingness to comply with the requirements of the study protocol
• Age \>= 18 years
• Have histologically confirmed World Health Organization grade IV glioma (glioblastoma or gliosarcoma). Archival tissue will be required for diagnosis confirmation. Receipt of archival tissue is not required for the start of treatment
• Patients must have been previously treated with radiation and temozolomide
• Patients must be at least 12 weeks out from completion of concurrent chemoradiation
• Have a performance status of \>= 60 on the Karnofsky performance status (KPS)
• Patients at either first or second recurrence will be considered eligible
• A baseline brain magnetic resonance imaging (MRI) obtained no more than 14 days prior to study enrollment
• Absolute neutrophil count (ANC) \>= 1,500 /mcL
• Platelets \>= 100,000 /mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Creatinine clearance should be calculated per institutional standard
• Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol) OR 24 hour (h) urine protein =\< 1g

You may not qualify if:

• Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery. Prior treatment with Gliadel wafers will be excluded. Active treatment with the Optune device will be excluded
• Has received radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment
• Has clinically relevant ongoing complications from prior radiation therapy
• Is currently participating in any other recurrent therapeutic trial after completion of chemoradiation
• Has history of cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
• Any serious medical condition that interferes with adherence to study procedures
• Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0)
• Has known leptomeningeal disease, gliomatosis cerebri, extracranial disease, or multifocal disease. Subject has multifocal glioblastoma (GBM), defined as discrete sites of contrast enhancing disease without contiguous T2/fluid attenuated inversion recovery (FLAIR) abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted
• Has history of interstitial lung disease or active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit
• Contraindication for undergoing MRIs
• Inability to comply with study and follow-up procedures

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

atezolizumab; cabozantinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Shiao-Pei S Weathers

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva Gachimova

CONTACT

(713) 794-4197; egachimova@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 9, 2021
• Study Start: September 23, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

US (1)