Immunotherapy + Radiation for Cancer

Recruiting at 293 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmunity, Active malignancy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase II trial studies how well pembrolizumab with or without stereotactic body radiation therapy works in treating patients with Merkel cell cancer that has spread to other places in the body (advanced). 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. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work better in treating patients with Merkel cell cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that patients with controlled brain metastases must be off steroids for at least 2 weeks before enrolling. It's best to discuss your specific medications with the trial team.

Is the combination of immunotherapy and radiation generally safe for humans?

Pembrolizumab (Keytruda), an immunotherapy drug, has been approved for use in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, and more serious immune-related issues such as pneumonitis (lung inflammation) and thyroid problems. When combined with radiation therapy, there may be an increased risk of immune-related side effects, so it's important for doctors to monitor patients closely. ^{1 2 3 4 5}

How is the treatment of pembrolizumab plus radiation for cancer different from other treatments?

This treatment combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with radiation therapy, which can enhance the immune response against tumors. This combination aims to improve the effectiveness of treatment by using the immune-boosting effects of both therapies together. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment combining pembrolizumab and radiation therapy for cancer?

Research suggests that combining pembrolizumab, an immune-boosting drug, with radiation therapy may enhance the body's ability to fight cancer by improving immune responses. This combination has shown potential benefits in various cancers, such as breast and gastroesophageal cancers, by possibly working together to better target and destroy cancer cells. ^{6 9 10 11 12}

Who Is on the Research Team?

Jason J Luke

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced Merkel Cell Carcinoma (MCC) who are in fairly good health, as shown by their ECOG status and normal organ function tests. They must have at least two cancerous deposits suitable for the study treatments and cannot be pregnant or nursing. People with HIV can join if they meet certain health criteria.

Inclusion Criteria

Your blood urea nitrogen level should be less than or equal to 30 mg/dl.

Your diastolic blood pressure is less than or equal to 90 mm Hg.

I am not pregnant or nursing and, if capable of becoming pregnant, I have a recent negative pregnancy test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 2 years. Group II also undergoes stereotactic body radiation therapy (SBRT) for 3 doses during cycle 1.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 6 months for up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing whether adding Stereotactic Body Radiation Therapy to Pembrolizumab, an immunotherapy drug, improves outcomes in patients with MCC. Participants will either receive just Pembrolizumab or both treatments together to see which works better.

How Is the Trial Designed?

Group I: Group II (pembrolizumab, SBRT) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SBRT for 3 doses during cycle 1.

Group II: Group I (pembrolizumab) Active Control 1 Intervention

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 14 patients with metastatic gastroesophageal cancer, combining palliative radiation therapy with the PD-1 inhibitor pembrolizumab resulted in an objective response rate of 28.6%, indicating potential effectiveness in this challenging cancer type.

While the combination therapy showed promising durable responses, the study did not find significant changes in PD-L1 expression that could explain the observed effects, suggesting that further research is needed to identify other biomarkers that may predict patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses. Chao, J., He, TF., D'Apuzzo, M., et al.[2022]

The combination of localized radiotherapy and immune checkpoint inhibitors, like pembrolizumab, may enhance the immune response against tumors, particularly in metastatic melanoma, but clinical data on this combination is limited.

A case report indicates that pembrolizumab may cause acute skin radiosensitization when used with radiation therapy, suggesting a rapid interaction that warrants caution in prescribing this combination for advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute skin reaction suggestive of pembrolizumab-induced radiosensitization. Sibaud, V., David, I., Lamant, L., et al.[2015]

In a study involving 8 patients with hormone receptor-positive metastatic breast cancer, combining pembrolizumab with palliative radiation therapy did not result in any objective responses, leading to the study's closure.

The median progression-free survival was only 1.4 months and overall survival was 2.9 months, indicating limited efficacy of this treatment combination in heavily pre-treated patients, although the treatment was generally safe with only one significant adverse event reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Barroso-Sousa, R., Krop, IE., Trippa, L., et al.[2021]

In a phase II study involving 18 patients with metastatic colorectal cancer, both low-dose fractionated radiation (LDFRT) and hypofractionated radiation (HFRT) were found to be feasible and safe when combined with PD-L1/CTLA-4 blockade, although 84% of patients experienced treatment-related toxicity.

The best treatment response was stable disease in one patient, and the study did not show significant efficacy in terms of tumor shrinkage outside the radiation field, suggesting that while the combination impacts the immune microenvironment, it may not be effective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer. Monjazeb, AM., Giobbie-Hurder, A., Lako, A., et al.[2022]

Pembrolizumab, an immunotherapy targeting PD-1, showed limited effectiveness in a patient with metastatic renal cell carcinoma, highlighting that only 20-40% of patients benefit from such treatments due to individual tumor biology and immune checkpoint diversity.

The patient's rapid disease progression during treatment may be linked to a lack of tumor-infiltrating lymphocytes (TILs) and the specific radiation dose and schedule used, which could affect the tumor microenvironment and the potential synergy with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. Alexander, GS., Palmer, JD., Tuluc, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., 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]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

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

A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses. [2022]

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

Acute skin reaction suggestive of pembrolizumab-induced radiosensitization. [2015]

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

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. [2021]

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

A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer. [2022]

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

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. [2022]

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

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

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

11. 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]

12. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]