Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adrenocortical Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Endocrine System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Atezolizumab

Epinephrine

Racepinephrine

Epinephryl borate

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 of each cycle and Atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) at screening and then every 12 weeks on study and undergo collection of blood samples at screening, on study, and at end of treatment. Patients without archival tissue also undergo biopsy at screening.

Biospecimen Collection

Cabozantinib S-malate

Computed Tomography

Magnetic Resonance Imaging

Bassel Nazha, MD, MPH

Wilena Session

This phase II trial tests how well cabozantinib in combination with atezolizumab works in treating patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), that has spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Cabozantinib inhibits receptor tyrosine kinases, which are receptors commonly over-expressed by tumor cells. This may result in an inhibition of both tumor growth and blood vessel formation, eventually leading to a decrease in tumor size or extent in the body. 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. Adding cabozantinib to atezolizumab may be more effective at treating patients with adrenal cortical cancer than giving these drugs alone.

PRIMARY OBJECTIVE:

I. To evaluate the anti-tumor activity of the combination of cabozantinib S-malate (cabozantinib) and Atezolizumab by assessing the overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.).

SECONDARY OBJECTIVE:

I. To evaluate the efficacy of the combination of cabozantinib and Atezolizumab as measured by progression free survival and overall survival assessed up to 2 years, safety and tolerability of the combination.

TERTIARY/EXPLORATORY OBJECTIVE:

I. To assess tissue-based assays in archival tissue and correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and cytokines.

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 of each cycle and Atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) at screening and then every 12 weeks on study and undergo collection of blood samples at screening, on study, and at end of treatment. Patients without archival tissue also undergo biopsy at screening.

After completion of study treatment, patients are followed for 28 days and then up to 2 years

Cabozantinib in Combination With Atezolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer

Phase II Open Label, Single-Arm Study of Cabozantinib in Combination With Atezolizumab in the Treatment of Locally Advanced or Metastatic Adrenocortical Carcinoma

Overall response rate is defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors version 1.1. Overall response rate will be estimated by the Clopper-Pearson method with 95% confidence intervals. Descriptive statistics on continuous data will include means, medians, standard deviations, and ranges, while categorical data will be summarized using frequency counts and percentages. Will explore whether the sample size can inform on the association between overall response rate and demographics or molecular biomarkers by Fisher's exact test -categorical variables and Wilcoxon rank-sum test -continuous variables, wherever appropriate this analysis is exploratory in nature.

The Kaplan-Meier method will be used to estimate median event time with 95% confidence interval.

Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Safety endpoints will be tabulated using frequency such as percent with at least one adverse event, percent for each grade, and percent with grade 3 or more adverse events.

National Cancer Institute (NCI)

Emory University

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Cabozantinib in Combination With Atezolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer	NCT06006013	Locally Advance... Adrenal Cortica... Stage III Adren... Stage IV Adrena... Unresectable Ad...	Atezolizumab Biospecimen Col... Cabozantinib S-... Computed Tomogr... Magnetic Resona...	18 Years -	Emory University
Cabozantinib in Combination With Atezolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer	NCT06006013	Locally Advance... Adrenal Cortica... Stage III Adren... Stage IV Adrena... Unresectable Ad...	Atezolizumab Biospecimen Col... Cabozantinib S-... Computed Tomogr... Magnetic Resona...	18 Years -	Emory University

Spots Global Cancer Trial Database for stage iv adrenal cortex carcinoma ajcc v8