Cabozantinib + Atezolizumab for Adrenocortical Cancer

Recruiting at 1 trial location

Overseen By Bassel Nazha, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Mitotane, Anticoagulants, Immunosuppressants, others

Disqualifiers: Brain metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 21 days per cycle, repeated until disease progression or unacceptable toxicity

21 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take mitotane and certain anticoagulants. Mitotane must be stopped 28 days before starting the trial, and some blood thinners are not allowed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Cabozantinib and Atezolizumab for treating adrenocortical cancer?

While there is no direct evidence for the combination of Cabozantinib and Atezolizumab in adrenocortical cancer, Cabozantinib is a type of drug known as a tyrosine kinase inhibitor, which has shown promise in other cancers by blocking signals that tumors use to grow. Atezolizumab is an immunotherapy drug that helps the immune system attack cancer cells, and similar drugs have improved outcomes in other types of cancer. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Atezolizumab safe for humans?

Cabozantinib, also known as Cabometyx, is approved for use in advanced kidney cancer, liver carcinoma, and medullary thyroid carcinoma, indicating it has been evaluated for safety in humans. Atezolizumab, also known as Tecentriq, is an immunotherapy drug used for various cancers, suggesting it has undergone safety testing in humans as well. ^{4 5 6 7 8}

How is the drug combination of Cabozantinib and Atezolizumab unique for treating adrenocortical cancer?

The combination of Cabozantinib and Atezolizumab is unique for treating adrenocortical cancer because it targets multiple pathways involved in tumor growth, with Cabozantinib inhibiting several proteins that promote cancer cell survival and Atezolizumab enhancing the immune system's ability to fight cancer. This approach is novel compared to traditional treatments like mitotane and chemotherapy, which have limited effectiveness and significant side effects. ^{3 5 8 9 10}

What is the purpose of this trial?

This phase II trial tests how well cabozantinib in combination with pembrolizumab 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 pembrolizumab, 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 pembrolizumab may be more effective at treating patients with adrenal cortical cancer than giving these drugs alone.

Research Team

Bassel Nazha, MD, MPH

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

Adults with advanced or inoperable adrenal cortical cancer, who may have had previous treatments. They must be physically able to perform daily activities (ECOG <=2), expect to live at least 12 weeks, and not have certain viral infections. Women of childbearing age need a negative pregnancy test and agree to use effective contraception.

Inclusion Criteria

My cancer is confirmed to be adrenal cortical carcinoma.

You have a measurable tumor that can be evaluated using specific criteria for assessing its size.

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I am currently taking mitotane.

I am currently on medication for hepatitis B.

You have a severe wound that won’t heal, problems with absorbing nutrients, untreated low thyroid function, serious liver problems, need for dialysis, recent organ transplant, history of severe infection, recent major surgery, certain heart rhythm problems, pregnancy or breastfeeding, difficulty swallowing pills or getting injections, allergies to study medications, or another active cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cabozantinib orally once daily and pembrolizumab intravenously every 21 days

21 days per cycle, repeated until disease progression or unacceptable toxicity

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

28 days initially, then up to 2 years

Regular follow-up visits

Treatment Details

Interventions

• Atezolizumab
• Cabozantinib

Trial Overview The trial is testing the combination of Cabozantinib, which blocks tumor growth signals, with Atezolizumab, an immunotherapy that helps the immune system fight cancer. The study aims to see if this combo is better than using each drug alone for treating adrenal cortical cancer.

Participant Groups

Group I: Treatment (cabozantinib, pembrolizumab) Experimental Treatment 5 Interventions

Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 of each cycle and pembrolizumab IV over 30 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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A patient with advanced adrenocortical carcinoma, which typically has a poor prognosis, showed a positive radiographical response after being treated with pembrolizumab and mitotane for 15 months following first-line chemotherapy.

The treatment was well-tolerated, with no severe adverse events reported, suggesting that pembrolizumab may be a safe and effective second-line therapy for patients with microsatellite instability-high tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response to pembrolizumab in microsatellite instability-high advanced adrenocortical carcinoma. Senda, M., Hashimoto, K., Shindo, T., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Activity and safety of temozolomide in advanced adrenocortical carcinoma patients. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Management of adrenocortical carcinoma: are we making progress? [2022]

3. England pubmed.ncbi.nlm.nih.gov

The role of mTOR pathway as target for treatment in adrenocortical cancer. [2020]

4. Ireland pubmed.ncbi.nlm.nih.gov

In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures&#9734;. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Durable response to pembrolizumab in microsatellite instability-high advanced adrenocortical carcinoma. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Objective Response and Prolonged Disease Control of Advanced Adrenocortical Carcinoma with Cabozantinib. [2023]

9. France pubmed.ncbi.nlm.nih.gov

[Adrenocortical carcinomas: therapeutic advances in 2011]. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Simulation-Based Interpretation of Therapeutically Monitored Cabozantinib Plasma Concentration in Advanced Adrenocortical Carcinoma with Hemodialysis. [2023]