Phase I/II Study to Evaluate the Safety and Clinical Efficacy of Atezolizumab (Anti-PD-L1) in Combination With Cabozantinib in Patients With Recurrent Glioblastoma (rGBM)
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Recurrent Glioblastoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Objective response rate
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of atezolizumab in combination with cabozantinib. (Phase I) II. To evaluate the progression-free survival at six months (PFS-6) of atezolizumab in combination with cabozantinib. (Phase II) SECONDARY OBJECTIVE: I. To evaluate the progression free survival (PFS), overall survival (OS), overall response rate (ORR) and duration of response of atezolizumab in combination with cabozantinib. CORRELATIVE OBJECTIVES: I. Profiling tumor immune cell populations (i.e., macrophage migration inhibitory factor \[mIF\] and immunohistochemistry \[IHC\] analyses of CD4, CD8, PD1, PD-L1, and PD-L2 expression). II. Profiling of tumor, e.g., deoxyribonucleic acid (DNA), messenger (m) ribonucleic acid (RNA), microRNA and epigenetic profiling (DNA methylation), whole exome sequencing, RNA sequencing, and microRNA sequencing. III. Peripheral blood collection for evaluation of circulating chemokines/cytokines. IV. Stool collection for gut microbiome profiling. OUTLINE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 and cabozantinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Treatment (atezolizumab, cabozantinib)
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.
Intervention: Atezolizumab
Treatment (atezolizumab, cabozantinib)
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.
Intervention: Cabozantinib
Outcomes
Primary Outcomes
Objective response rate
Time Frame: Up to 3 years
Will be estimated with exact binomial 95% confidence intervals. Logistic regression will be used to explore the correlations between response rates and correlative markers.
Progression-free survival (PFS)
Time Frame: At 6 momths
Will estimate the 6 months PFS distribution using the Kaplan-Meier method.
Incidence of adverse events
Time Frame: Up to 3 years
Will be estimated with exact binomial 95% confidence intervals. Adverse events will be tabulated by grade and by their relationship to the treatment.