Cabozantinib + Cemiplimab for Adrenal Cancer

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Autoimmune disease, Hypertension, Cardiac 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: Unknown

Duration: 2 years

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two treatments, cabozantinib and cemiplimab, for individuals with adrenocortical cancer that cannot be surgically removed or has spread. Cabozantinib stops cancer cell growth, while cemiplimab enhances the immune system to attack cancer. Participants will receive either cabozantinib alone or a combination of cabozantinib and cemiplimab. This trial may suit those with adrenocortical cancer that has spread or returned and who have not previously received these specific drugs. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. If you have been taking mitotane, you need to stop it 28 days before joining the study. Also, you must stop taking strong CYP3A4 inhibitors and inducers 14 days before starting the trial. Herbal supplements and certain blood thinners like warfarin must be stopped 5 days before joining.

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

Research has shown that cabozantinib has a promising safety record for treating advanced adrenocortical carcinoma. In some studies, serious side effects such as high blood pressure and changes in liver function occurred in about 20.8% of patients. While these side effects are significant, they are considered manageable and expected with this type of treatment.

Less detailed information exists about the combination of cabozantinib and cemiplimab. However, cabozantinib alone has been well-tolerated in similar situations, suggesting that the combination might also be safe for many people. Ongoing studies are confirming this. Both treatments aim to stop cancer growth, and their safety is under close observation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cabozantinib and cemiplimab for adrenal cancer because these treatments offer a new approach compared to the traditional options like surgery, mitotane, or chemotherapy. Cabozantinib works by targeting specific pathways involved in tumor growth and blood vessel formation, potentially slowing down the cancer's progression. Cemiplimab is an immunotherapy that helps the body's immune system recognize and attack cancer cells more effectively. The combination of these treatments might enhance their effectiveness, providing a promising alternative to existing therapies.

What evidence suggests that this trial's treatments could be effective for adrenocortical cancer?

Studies have shown that cabozantinib, which participants in Arm A of this trial may receive, can effectively treat advanced adrenocortical carcinoma and is generally safe. In earlier research, 72.2% of patients did not experience cancer progression for at least four months. In Arm B of this trial, cabozantinib is combined with cemiplimab, which may lead to even better outcomes. This combination might enhance the immune system's ability to fight cancer cells. Early results suggest that this combo could slow cancer growth and potentially destroy more tumor cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Bhavana Konda

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adolescents and adults with advanced adrenocortical cancer that's locally advanced, can't be removed by surgery, has returned after treatment, or spread to other body parts. Participants must not have had prior treatments with cabozantinib or certain immunotherapies, should have measurable disease per RECIST v 1.1 criteria, and may have had up to three previous systemic therapies.

Inclusion Criteria

I have been diagnosed with adrenocortical carcinoma.

My cancer can be measured by standard health scans.

My cancer cannot be removed by surgery and has either spread or come back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cabozantinib with or without cemiplimab in cycles of 21 days for up to 2 years

2 years

Regular visits for CT/MRI and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 12 weeks until disease progression, then every 6 months for 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Cemiplimab

Trial Overview The study is testing the combination of Cabozantinib (a drug that blocks proteins signaling cancer cell growth) and Cemiplimab (an immunotherapy drug). The goal is to see if this combo is more effective in killing tumor cells than when each drug is used alone in patients with specific types of adrenocortical cancer.

How Is the Trial Designed?

Group I: Arm B (cabozantinib and cemiplimab) Experimental Treatment 5 Interventions

Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.

Group II: Arm A (cabozantinib) Experimental Treatment 4 Interventions

Patients receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38608694/

a single-arm, phase 2 trial - PubMed - NIH Interpretation: Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile.

2. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00095-0/abstract

Cabozantinib monotherapy for advanced adrenocortical ... Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further ...

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

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

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03612232

Study Details | NCT03612232 | Cabozantinib in Advanced ... Objective response rates were 23 and 9%. EDP plus mitotane is therefore considered as standard treatment of ACC. Results by Phan et al. (Cancer Research 2015) ...

5. ascopost.com ascopost.com/news/april-2024/cabozantinib-in-advanced-adrenocortical-carcinoma/

Cabozantinib in Advanced Adrenocortical Carcinoma A total of 13 patients (72.2%, 95% confidence interval [CI] = 46.5%–90.3%) had progression-free survival at 4 months. Median progression-free ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8204945/

Objective Response and Prolonged Disease Control of ... CABO monotherapy appears to be safe and effective as a monotherapy in advanced ACC after failing prior treatments.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1558767323002173

Real-World Results of Cabozantinib Given as Alternative ... Reasons for treatment discontinuations were disease progression, toxicity and death in 52.1%, 5.6%, and 9.9% of patients, respectively. Thirty-two percent of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06006013

Cabozantinib in Combination With Pembrolizumab for the ... Adding cabozantinib to pembrolizumab may be more effective at treating patients with adrenal cortical cancer than giving these drugs alone. Detailed Description.