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

Trial Summary

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.

What data supports the effectiveness of the treatment Radiotherapy + Pembrolizumab for Adrenocortical Cancer?

Research shows that pembrolizumab, when used with other treatments like mitotane, has led to partial or complete responses in some patients with advanced adrenocortical carcinoma. Additionally, combining radiotherapy with pembrolizumab has shown promise in controlling metastases and enhancing immune responses in similar cases. ^{1 2 3 4 5}

Is the combination of radiotherapy and pembrolizumab safe for humans?

Pembrolizumab, used in cancer treatment, can cause immune-related side effects like colitis (inflammation of the colon), gastroduodenitis (inflammation of the stomach and the beginning of the small intestine), pneumonitis (lung inflammation), and thyroiditis (inflammation of the thyroid gland). In rare cases, it can also lead to type 1 diabetes. Safety data for the combination with radiotherapy is limited, but some patients have experienced these side effects when treated with pembrolizumab. ^{1 2 4 6 7}

How does the treatment of radiotherapy combined with pembrolizumab differ from other treatments for adrenocortical cancer?

This treatment is unique because it combines ablative radiotherapy (a precise form of radiation therapy) with pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells. Unlike standard chemotherapy, this approach may enhance the body's immune response to cancer, offering a novel option for a condition with limited effective treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to determine whether pembrolizumab given after standard ablative Radiotherapy is a safe treatment that causes few or mild side effects in people with advanced Adrenocortical Carcinoma.

Research Team

Nitya Raj, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

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

Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. [2020]

2. Australia pubmed.ncbi.nlm.nih.gov

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

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

Complete Radiological Response of Recurrent Metastatic Adrenocortical Carcinoma to Pembrolizumab and Mitotane. [2021]

4. Germany 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. [2023]

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

Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer. [2020]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]