Radiotherapy + Pembrolizumab for Adrenocortical Cancer

Recruiting at 6 trial locations

Overseen By Rohit Thummalapalli, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Mitotane

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, 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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 1 year

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pembrolizumab, an immunotherapy drug, given after standard radiotherapy, is a safe treatment for individuals with advanced adrenocortical carcinoma, a cancer affecting the adrenal glands. Researchers aim to determine if this combination causes only mild or manageable side effects. The trial specifically seeks participants with adrenocortical carcinoma that has spread to the liver and other areas outside the liver. Participants should exhibit noticeable symptoms related to liver metastases and be able to engage in daily activities with minimal limitations. As a Phase 2 trial, this 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 does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these 7 days before starting the trial. If you are taking mitotane for hormonal symptoms, you can continue it during the study.

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

Research has shown that ablative radiotherapy, which uses precise, high doses of radiation to target tumors, is generally safe for patients with adrenal tumors. Side effects are usually mild and manageable. For instance, studies found that only 7.4% of patients experienced tumor growth in the treated area, suggesting the radiotherapy is effective and typically doesn't cause severe issues.

Studies have also examined the safety of pembrolizumab, a drug that helps the immune system fight cancer. In patients with advanced adrenocortical carcinoma, pembrolizumab was generally well-tolerated. However, some patients experienced side effects. About 17.9% had more serious reactions, though these were uncommon. A few patients had to stop taking the drug due to side effects, but it still showed potential benefits in treating the cancer.

Overall, previous studies have shown both treatments to be safe, though like any medical treatment, they do carry some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for adrenocortical cancer, which typically include surgery, chemotherapy, and mitotane, this new approach combines ablative radiotherapy with pembrolizumab, an immunotherapy drug. Pembrolizumab is particularly exciting because it works by unleashing the power of the immune system to attack cancer cells, which is a different mechanism than traditional chemotherapy. Additionally, ablative radiotherapy precisely targets and destroys cancerous tissues, potentially leading to fewer side effects and better outcomes. Researchers are hopeful that this combination will improve survival rates and quality of life for patients with metastatic adrenocortical carcinoma.

What evidence suggests that this trial's treatments could be effective for Adrenocortical Cancer?

This trial will evaluate the combination of ablative radiotherapy and Pembrolizumab for treating adrenocortical carcinoma. Studies have shown that ablative radiotherapy effectively targets and controls adrenal tumor growth with generally manageable side effects. Pembrolizumab has been tested in people with advanced adrenocortical carcinoma, and some patients experienced long-lasting positive results, such as cancer stabilization or reduction. While its effectiveness can vary, it has shown promise in managing advanced stages of this cancer. Overall, these treatments offer hopeful options for dealing with adrenocortical carcinoma. ^{2 4 5 6 7}

Who Is on the Research Team?

Nitya Raj, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced Adrenocortical Carcinoma (ACC) and liver metastases, ECOG performance status of 0, measurable disease, adequate organ function. Must not have had recent treatments or other cancers, no active infections or immunodeficiencies, and agree to contraception.

Inclusion Criteria

Be willing and able to provide written informed consent for the trial

You have a disease that can be measured using specific guidelines.

Consent for use of archived tissue for research purposes. Archival tissue (1 block or 20 unstained slides) will be requested, when available

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I have been diagnosed with HIV.

You have a currently active Hepatitis B or Hepatitis C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Participants receive standard ablative Radiotherapy

4-6 weeks

Treatment

Participants receive pembrolizumab following Radiotherapy

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ablative Radiotherapy
• Pembrolizumab

Trial Overview The trial is testing the safety and side effects of Pembrolizumab following ablative Radiotherapy in patients with ACC. The goal is to see if this combination treatment causes few or mild side effects.

How Is the Trial Designed?

Group I: Participants with Adrenocortical Carcinoma Experimental Treatment 2 Interventions

Participants with histologically proven metastatic Adrenocortical Carcinoma/ACC with both intra-hepatic and extra-hepatic sites of disease.

Ablative Radiotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as SABR/SBRT for:

• Lung cancer
• Prostate cancer
• Kidney cancer
• Liver cancer
• Bone metastases
• Spine metastases

Approved in United States as SABR/SBRT for:

• Lung cancer
• Prostate cancer
• Kidney cancer
• Liver cancer
• Bone metastases
• Spine metastases
• Brain tumors

Approved in Canada as SABR/SBRT for:

• Lung cancer
• Prostate cancer
• Kidney cancer
• Liver cancer
• Bone metastases
• Spine metastases

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a retrospective review of six patients with metastatic adrenocortical carcinoma (ACC) who had previously failed mitotane and chemotherapy, the combination of pembrolizumab and mitotane showed promising results, with two patients achieving partial responses and four maintaining stable disease for 8 to 19 months.

All patients lived for at least 16 months after starting the combination therapy, indicating potential efficacy, and the treatment appeared effective in both microsatellite instability-high and stable tumors, suggesting a possible synergistic effect with mitotane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer. Head, L., Kiseljak-Vassiliades, K., Clark, TJ., et al.[2020]

A 40-year-old woman with recurrent metastatic adrenocortical carcinoma (ACC) achieved a complete radiological response after 4 cycles of pembrolizumab combined with mitotane maintenance therapy, marking a significant treatment milestone.

This case suggests the potential efficacy of combining pembrolizumab, an immunotherapy, with mitotane in treating metastatic ACC, warranting further clinical trials to explore this combination's benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Radiological Response of Recurrent Metastatic Adrenocortical Carcinoma to Pembrolizumab and Mitotane. Alam, W., Bouferraa, Y., Haibe, Y., et al.[2021]

In three cases of advanced adrenocortical carcinoma (ACC) treated with high-dose rate brachytherapy (HDR-BT) and the immune checkpoint inhibitor pembrolizumab, two patients achieved complete responses and one had a partial response, indicating potential efficacy of this combination therapy after standard chemotherapy failure.

Despite the promising responses, immune-related adverse events were observed, including severe colitis and pneumonitis, highlighting the need for careful monitoring in patients receiving this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series. Schwarzlmueller, P., Corradini, S., Seidensticker, M., et al.[2023]

In a phase II clinical trial involving 16 patients with metastatic adrenocortical carcinoma (ACC), pembrolizumab showed a modest non-progression rate of 36% at 27 weeks, indicating some effectiveness as a salvage therapy.

The treatment was generally well tolerated, with only 13% of patients experiencing severe adverse events, suggesting that pembrolizumab may be a safe option for patients with ACC despite limited overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. Habra, MA., Stephen, B., Campbell, M., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

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]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2405630823001052

Clinical outcomes of MR-guided adrenal stereotactic ... MRgRT for adrenal metastases is well tolerated with high local control rates despite prioritizing OAR sparing over PTV coverage.

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Stereotactic radiotherapy as a valuable therapeutic procedure ... Stereotactic radiotherapy as a valuable therapeutic procedure for controlling aldosterone-secreting adrenocortical carcinoma.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1879850025001742

Stereotactic Body Radiation Therapy for the Treatment of ... This case-based guide and review provides a comprehensive overview of SBRT for treating adrenal tumors, specifically metastases.

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Clinical Outcomes of Online Adaptive Magnetic Resonance ... Online adaptive MR-guided radiotherapy improves tumor coverage and organ-at-risk sparing compared to non-adaptive radiotherapy.

5. nature.com nature.com/articles/s41598-020-64770-2

Clinical efficacy of Stereotactic Body Radiation Therapy ... SBRT is an effective therapeutic option for treatment of AGM with high LC rates with minimal toxicity.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7001286/

Stereotactic body radiotherapy (SBRT) for adrenal ... Results. During the period of review 28 patients received ablative SBRT to their adrenal gland metastases. Most common primary tumors were non- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10377531/

The Judicious Use of Stereotactic Ablative Radiotherapy in the ... This article discusses recent advances in the use of stereotactic ablation radiotherapy for localized renal cell carcinoma.