Radiotherapy + Checkpoint Inhibitor for Kidney Cancer

(SPARK Trial)

Overseen By RAQUIBUL HANNAN, MD, PhD.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Ultracentral chest lesions

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: 17

Duration: 12 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate progression of metastatic renal cell carcinoma from the initiation of PULSAR radiotherapy in combination with IMSA101 injectable onward.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Radiotherapy + Checkpoint Inhibitor for Kidney Cancer?

Research shows that combining PD-1 inhibitors (a type of drug that helps the immune system fight cancer) with radiotherapy can be effective in treating advanced kidney cancer. Additionally, immune checkpoint inhibitors like nivolumab and ipilimumab have been successful in treating metastatic renal cell carcinoma, suggesting potential benefits for similar treatments. ^{1 2 3 4 5}

Is the combination of radiotherapy and checkpoint inhibitors safe for treating kidney cancer?

Immune checkpoint inhibitors, which are part of the treatment, can cause immune-related side effects, but these are often linked to better outcomes in kidney cancer patients. The overall safety of these treatments has been studied, but specific safety data for the combination with radiotherapy is not detailed in the available research. ^{2 6 7 8 9}

How is the treatment with IMSA101 different from other kidney cancer treatments?

The treatment combines radiotherapy with a checkpoint inhibitor, which is unique because it uses the body's immune system to fight cancer cells while also targeting them with radiation. This combination may enhance the effectiveness of the immune response against kidney cancer, which is traditionally considered resistant to radiation alone. ^{1 5 10 11 12}

Research Team

RAQUIBUL HANNAN, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for individuals with metastatic renal cell carcinoma, a type of kidney cancer that has spread to other parts of the body. Specific eligibility criteria are not provided, so it's important to contact the study organizers for detailed requirements.

Inclusion Criteria

My cancer has spread to 3 or fewer places.

My organ and bone marrow functions are within normal ranges.

All IMDC risk categories are allowed

Exclusion Criteria

My cancer has not spread to the center of my chest.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PULSAR radiotherapy and IMSA101 injections in combination with Nivolumab

12 weeks

5 visits for IMSA101 injections, monthly visits for Nivolumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Follow-up visits every 12 weeks

Long-term follow-up

Participants are contacted every 3 months for survival data

Up to 4 years

Treatment Details

Interventions

• IMSA101
• Radiotherapy

Trial Overview The trial is testing the effectiveness of PULSAR radiotherapy when combined with an injectable treatment called IMSA101 in slowing down or stopping the progression of metastatic kidney cancer.

Participant Groups

Group I: SAbR with Intratumoral STING agonist IMSA101 and IO with Anti-PD1 Experimental Treatment 1 Intervention

Only one arm will be maintained in this phase II study with all patients undergoing the following treatment: SOC treatment: Nivolumab 480 mg monthly PULSAR: 36 Gy in 3 fractions, Q4weeks IMSA101: five intra-tumoral injections of one of the progressive lesions at 1200 mcg (C1D1, C1D8, C1D15, C2D1, C3D1)

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

The combination of ipilimumab and nivolumab has been approved as the first dual checkpoint inhibitor therapy for treatment-naïve patients with intermediate to poor risk metastatic renal cell carcinoma (mRCC), marking a significant advancement in immunotherapy for this cancer.

This review discusses the trials that led to the approval of this combination therapy and highlights ongoing research, indicating a strong focus on optimizing treatment for various patient populations and addressing remaining clinical questions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and Nivolumab as First-Line Treatment of Patients with Renal Cell Carcinoma: The Evidence to Date. Sheng, IY., Ornstein, MC.[2020]

Lenvatinib plus pembrolizumab had the highest rates of severe treatment-related adverse events (grade ≥3 TRAEs) and treatment discontinuation among the combination therapies for advanced renal cell carcinoma.

Nivolumab plus ipilimumab had the lowest rates of severe TRAEs but was linked to more endocrine-related adverse events, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. Quhal, F., Mori, K., Remzi, M., et al.[2023]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Predictive Impact of Peripheral Blood Markers and C-Reactive Protein in Nivolumab Therapy for Metastatic Renal Cell Carcinoma. [2020]

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

Adjuvant immunotherapy in renal cell carcinoma: a systematic review and meta-analysis. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab and Nivolumab as First-Line Treatment of Patients with Renal Cell Carcinoma: The Evidence to Date. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Predictive Value of Programmed Death Ligand 1 in Patients with Metastatic Renal Cell Carcinoma Treated with Immune-checkpoint Inhibitors: A Systematic Review and Meta-analysis. [2022]

5. Egypt pubmed.ncbi.nlm.nih.gov

Clinical Efficacy of PD-1 Inhibitors Plus Split-Course Radiotherapy in the First-Line Treatment of Advanced Kidney Cancer: A Randomized Controlled Trial. [2022]

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

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. [2023]

7. France pubmed.ncbi.nlm.nih.gov

Comparison of the Impact of Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Dual Combination Therapy and Immune Checkpoint Inhibitor Plus Tyrosine Kinase Inhibitor Combination Therapy in Patients with Advanced Renal Cell Carcinoma. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Association between Immune Related Adverse Events and Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors. [2021]

10. Australia pubmed.ncbi.nlm.nih.gov

Possible abscopal effect after discontinuation of nivolumab in metastatic renal cell carcinoma. [2022]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Combining Radiotherapy with Immunocheckpoint Inhibitors or CAR-T in Renal Cell Carcinoma. [2021]

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

Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade. [2023]