Cabozantinib + Atezolizumab for Adrenocortical Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced or inoperable adrenocortical cancer. Researchers aim to determine how effectively the drugs cabozantinib and atezolizumab (Tecentriq) work together to halt cancer growth and spread. Cabozantinib may reduce tumor size by blocking specific signals in cancer cells, while atezolizumab could enhance the immune system's ability to attack the cancer. The trial seeks participants with adrenocortical cancer that has spread or cannot be surgically removed and who have measurable disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cabozantinib has a manageable safety record in patients with advanced adrenocortical carcinoma. One study found that the safety results aligned with those from other trials, revealing no unexpected serious side effects. Some patients experienced common lab test changes, but these were anticipated.

For atezolizumab, studies have found it can cause immune-related side effects, such as pneumonitis (inflammation of the lungs) and infections. However, these side effects were not frequent enough to discontinue the treatment in similar cases.

Both treatments have a known safety profile, indicating that doctors understand the potential side effects. While risks remain, the treatments are generally well-tolerated in similar patient groups. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using cabozantinib and atezolizumab for adrenocortical cancer because they bring a fresh approach compared to current treatments. Cabozantinib targets growth pathways in cancer cells, potentially stopping their spread more effectively. Atezolizumab, on the other hand, is an immunotherapy that helps the body's immune system recognize and attack cancer cells. This combination could offer a new way to tackle adrenocortical cancer, which is challenging to treat with existing options like surgery, radiation, or chemotherapy alone.

What evidence suggests that cabozantinib and atezolizumab might be effective for adrenocortical cancer?

Research has shown that the combination of cabozantinib and atezolizumab has some effect in treating advanced adrenocortical cancer (ACC). In one study, about 8% of patients experienced a noticeable decrease in tumor size. However, approximately one-third of the patients achieved disease control, meaning their cancer did not worsen for a period. Cabozantinib blocks signals that help tumors grow, while atezolizumab enhances the immune system's ability to attack cancer cells. This trial will evaluate cabozantinib in combination with pembrolizumab, another immune checkpoint inhibitor, to assess its potential effectiveness in treating ACC. ^{6 7 8 9 10}

Who Is on the Research Team?

Bassel Nazha, MD, MPH

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.1

Cabozantinib plus atezolizumab in locally advanced/ ... Conclusions: Cabozantinib plus atezolizumab showed modest activity in locally advanced/metastatic ACC. Safety profile was consistent with ...

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-penile-urethral-testicular-and-adrenal-cancers/149432-asco-gu-2024-cabozantinib-plus-atezolizumab-in-locally-advanced-metastatic-adrenocortical-carcinoma-results-from-a-multi-cohort-basket-phase-ii-trial-cabaten-getne-t1914.html

ASCO GU 2024: Cabozantinib plus Atezolizumab in ... For the primary outcome of ORR, only 2/26 patients (8.3%) achieved an ORR. The disease control rate 33.3%, with a median duration of response of ...

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-detailed-results-phase-3-contact-02-pivotal

Exelixis Announces Detailed Results of Phase 3 CONTACT ... Cabozantinib in combination with atezolizumab reduced the risk of disease progression or death by 35% in patients with metastatic castration-resistant prostate ...

4. cancernetwork.com cancernetwork.com/view/second-line-cabozantinib-regimens-exhibit-efficacy-in-advanced-rcc

Second-Line Cabozantinib Regimens Exhibit Efficacy in ... Additional efficacy data revealed that in the monotherapy and combination arms, the ORR was 36% vs 37%, all of which consisted of PRs. Among ...

5. onclive.com onclive.com/view/cabozantinib-plus-atezolizumab-in-locally-advanced-metastatic-adrenocortical-carcinoma-results-from-a-multi-cohort-basket-phase-ii-trial-cabaten-getne-t1914-

Results From a Multi-Cohort Basket Phase II Trial ... The results of a multi-cohort basket phase II trial, CABATEN/GETNE-T1914, evaluating cabozantinib plus atezolizumab in patients with locally advanced/ ...

6. tecentriq-hcp.com tecentriq-hcp.com/metastatic-nsclc/side-effects/important-safety-information.html

Important Safety Information | TECENTRIQ® (atezolizumab) TECENTRIQ can cause immune-mediated pneumonitis. · Immune-mediated pneumonitis occurred in 3% (83/2616) of patients receiving TECENTRIQ alone, including fatal (< ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/761034s010lbl.pdf

TECENTRIQ (atezolizumab) injection - accessdata.fda.gov In clinical studies enrolling 2616 patients with various cancers who received TECENTRIQ [see Adverse Reactions (6.1)], infections occurred in 42% of patients, ...

8. tecentriq.com tecentriq.com/safety.html

Important Safety Information | TECENTRIQ® (atezolizumab) TECENTRIQ can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work.

9. tecentriq.global tecentriq.global/home/safety-profile.html

Safety profile - tecentriq Review the safety profile of TECENTRIQ monotherapy and combination therapy in clinical trials, including the most commonly reported adverse reactions.

10. gene.com gene.com/medical-professionals/medicines/tecentriq

Tecentriq® (atezolizumab) - Information for Healthcare ... TECENTRIQ can cause primary or secondary adrenal insufficiency. · Adrenal insufficiency occurred in 0.4% (11/2616) of patients receiving TECENTRIQ alone, ...