Maintenance Therapy After Radiation for Renal Cell Carcinoma

Overseen By Chad Tang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: HIV, Organ transplant, Pregnancy, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding pembrolizumab, a type of immunotherapy, for one year can help control renal cell carcinoma (RCC) after radiation therapy. It involves two groups: one receiving only radiation therapy and the other receiving both radiation therapy and pembrolizumab. This study suits individuals with RCC that includes a clear cell component and who have five or fewer metastatic lesions treatable with radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in RCC treatment.

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 immunotherapy, you must have stopped it at least 24 weeks before starting radiation, and if on other systemic therapies, at least 4 weeks before. 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 pembrolizumab has been tested for safety in people with kidney cancer. One study found that serious side effects occurred in about 50% of participants. Common issues included high blood pressure and urinary tract infections, affecting about 4.4% and 3.2% of people, respectively.

The FDA has already approved pembrolizumab for treating some other types of cancer, providing a wealth of safety information. However, individual responses can vary, so discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for renal cell carcinoma because they explore the potential of combining radiation therapy with pembrolizumab, a type of immunotherapy. Unlike traditional treatments, such as surgery and targeted therapies that focus on the cancer cells themselves, pembrolizumab works by boosting the body's immune system to better recognize and attack cancer cells. This combination could enhance the effectiveness of radiation therapy by potentially reducing the risk of cancer recurrence. This innovative approach aims to improve patient outcomes, offering hope for a more effective maintenance strategy post-radiation.

What evidence suggests that this trial's treatments could be effective for renal cell carcinoma?

This trial will compare the effects of radiation therapy alone with radiation therapy followed by pembrolizumab. Research has shown that pembrolizumab, when used after kidney cancer surgery, can help patients remain cancer-free for longer. In one study, 77.3% of participants who took pembrolizumab were cancer-free after 24 months, compared to those who did not take the drug. Another study found that pembrolizumab reduced the risk of death by 38% compared to a placebo group. These results suggest that pembrolizumab could help control kidney cancer after radiation therapy. ^{1 5 6 7 8}

Who Is on the Research Team?

Chad Tang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific kidney cancer (RCC) that has spread to no more than five places. They must have good organ function, not be on immunosuppressants or have had severe reactions to immune checkpoint inhibitors before, and can't be pregnant.

Inclusion Criteria

My cancer can be measured and has grown in previously treated areas.

I am willing to have a biopsy, or I already had one that can be used for this study.

My recent tests show my organs are functioning well.

Exclusion Criteria

My doctor thinks I can't understand or follow the study due to cognitive issues.

I have not received a live vaccine within the last 30 days.

I do not have conditions that weaken my immune system, such as HIV or a history of organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive definitive radiation therapy

4-6 weeks

Maintenance Therapy

Participants receive 1 year of pembrolizumab or are observed

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Radiation Therapy

Trial Overview The study tests if pembrolizumab, an immune therapy drug, helps control RCC when given for a year after radiation therapy. Patients are randomly chosen to receive either the drug plus radiation or radiation alone.

How Is the Trial Designed?

Group I: Radiation therapy (Control Arm) Experimental Treatment 2 Interventions

Participants will be asked to receive radiation therapy and be randomly assigned to receive pembrolizumab or not after that.

Group II: Radiation Therapy and Pembrolizumab Experimental Treatment 2 Interventions

Participants will be asked to receive radiation therapy and be randomly assigned to receive pembrolizumab or not after that.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Published Research Related to This Trial

A new three-step protocol combining surgery with intraoperative radiotherapy (IORT) and an external boost of 40 Gy was tested on six patients with local recurrences of renal cell carcinoma, showing no increase in side effects or morbidity.

One year after treatment, there were no recurrences in the radiation field, suggesting that this protocol may be effective for patients with solitary local recurrences and advanced tumors (clinical stage T3 and T4).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraoperative electron irradiation (IORT) of urologic tumors. Initial results of a pilot study of local recurrences of renal cell cancers]. Beer, M., Eble, MJ., Wannenmacher, M., et al.[2006]

Stereotactic radiation therapy (SRT) demonstrated high local control rates for metastatic renal cell carcinoma (RCC), with 87.5% at 6 months and 77.6% at 24 months, indicating its effectiveness in managing this typically radioresistant cancer.

The treatment was found to be safe, with only 2.6% of patients experiencing severe toxicities, and it may help delay the need for systemic therapy, suggesting a potential benefit in the overall management of RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy in the strategy of treatment of metastatic renal cell carcinoma: A study of the Getug group. Meyer, E., Pasquier, D., Bernadou, G., et al.[2019]

Radiotherapy (RT) can effectively reduce the risk of local recurrence in patients with renal-cell carcinoma (RCC) after surgery and offers excellent outcomes for those who are not fit for surgical procedures.

The review highlights various RT techniques, including conventional RT, intraoperative radiotherapy, and stereotactic body radiotherapy, suggesting that these methods should be further explored in clinical trials to optimize treatment for RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Role of Radiotherapy for Renal-Cell Carcinoma: Review. Dengina, N., Tsimafeyeu, I., Mitin, T.[2018]

Adaptive MR-guided radiotherapy (MRgRT) shows promise as a non-invasive treatment for renal cell carcinoma, with early clinical experiences indicating improved target coverage and reduced damage to surrounding healthy tissues.

Technological advancements in MRgRT are expected to address challenges related to organ motion, potentially leading to better treatment outcomes and preservation of kidney function in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy: The Next Step in the Treatment of Renal Cell Carcinoma. Keller, B., Bruynzeel, AME., Tang, C., et al.[2021]

Intraoperative radiotherapy (IORT) was used in 11 patients with locally advanced or recurrent renal cell carcinoma, achieving 100% local tumor control despite the challenges of radioresistance and incomplete tumor resection.

The treatment resulted in a low rate of therapy-related side effects, with no specific late adverse effects from IORT, suggesting it is a promising approach for improving local control in renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The intraoperative radiotherapy (IORT) of locally spread and recurrent renal-cell carcinomas]. Eble, MJ., Staehler, G., Wannenmacher, M.[2019]

Stereotactic body radiotherapy (SBRT) for localized renal cell carcinoma (RCC) was well-tolerated in 19 patients aged 59-89, with no dose-limiting toxicities observed at doses up to 48Gy in 4 fractions.

Among the patients treated, 3 showed a partial response and 12 had stable disease, indicating that SBRT can be an effective treatment option for patients who are poor surgical candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. Ponsky, L., Lo, SS., Zhang, Y., et al.[2022]

In a study of 74 patients with metastatic renal cell carcinoma, adding stereotactic body radiotherapy (SBRT) to non-first-line PD-1 inhibitors and targeted agents significantly improved overall survival, with a median of 38.5 months compared to 15.4 months for those receiving only anti-PD-1/TA therapy.

The combination of SBRT with anti-PD-1/TA therapy was found to be safe and tolerable, with a similar rate of severe toxicities (54.8% in the SBRT group vs. 65.6% in the anti-PD-1/TA alone group), suggesting that this approach could be beneficial for patients, especially those with clear-cell type renal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma. Liu, Y., Zhang, Z., Liu, R., et al.[2023]

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

A 56-year-old woman with recurrent renal cell carcinoma showed significant reduction in multiple metastases after receiving conventional palliative radiotherapy following 22 cycles of nivolumab, an immune checkpoint inhibitor.

This case suggests that combining radiotherapy with immune checkpoint inhibitors may produce systemic effects, potentially leading to an abscopal effect, where localized treatment impacts distant metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible abscopal effect after discontinuation of nivolumab in metastatic renal cell carcinoma. Nakajima, N., Kano, T., Oda, K., et al.[2022]

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma (RCC) showed excellent local control rates of 98.1% at 1 year and 91.9% at 3 years, with a median follow-up of 28.3 months for 46 patients.

The treatment was associated with low toxicity and improved overall survival, particularly in patients receiving a biologically effective dose (BEDiso) of 130 Gy or more, highlighting the potential efficacy of high-dose SBRT in managing RCC metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma-a multicenter analysis of the German working group "Stereotactic Radiotherapy". Hoerner-Rieber, J., Duma, M., Blanck, O., et al.[2022]

In a phase 1 study involving 13 patients with primary renal cell carcinoma, the maximum tolerated dose of stereotactic body radiation therapy (SBRT) was determined to be 12 Gy given in 4 fractions, with no dose-limiting toxicities observed.

After 24 months of follow-up, patients experienced no significant renal function decline, and while two patients showed a partial response, the majority maintained stable disease, indicating the treatment's safety and potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Cancer: 24-Month Results of the RSR1 Phase 1 Dose Escalation Study. Lapierre, A., Badet, L., Rouviere, O., et al.[2023]

Stereotactic ablative radiotherapy (SABR) has emerged as a promising treatment for renal cell carcinoma (RCC), showing excellent tumor control in both primary RCC and metastatic cases, thanks to its ability to deliver high doses of radiation safely.

Recent studies suggest that combining SABR with immunotherapies may enhance treatment effectiveness by stimulating antitumor immunity, marking a significant shift in the role of radiotherapy in RCC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for renal cell carcinoma: renaissance of an overlooked approach. Siva, S., Kothari, G., Muacevic, A., et al.[2022]

Citations

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Open-Label, Single-Arm Phase II Study of Pembrolizumab ... Efficacy Outcomes in the Total Population. The ORR was 36.4% (95% CI ... : Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.

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Advanced Renal Cell Carcinoma: Efficacy and Safety Results Health care professionals can review efficacy data and safety results for a first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

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Safety and Efficacy Study of Pembrolizumab (MK-3475) as ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.LBA359

Overall survival results from the phase 3 KEYNOTE-564 ... Adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo following nephrectomy in participants (pts) with ccRCC at an increased risk ...

8. keytruda.com keytruda.com/kidney-cancer/adjuvant-clinical-trial-results/

results from a clinical trial. In the clinical trial, more people receiving KEYTRUDA after surgery did not have their kidney cancer (RCC) return or spread compared to people receiving ...