Nivolumab with Surgery for Kidney Cancer

(PROSPER Trial)

Recruiting at 471 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Liver disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 17

Duration: Approximately 20 weeks

819 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, you must not be on any systemic treatment with corticosteroids or other immunosuppressive medications, except for certain exceptions like topical or inhaled steroids. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Nivolumab with surgery for kidney cancer?

Research shows that Nivolumab, when used before surgery, is safe and feasible for patients with localized kidney cancer, allowing them to proceed with surgery without significant delays. Additionally, there are cases where Nivolumab has led to a complete response in patients with advanced kidney cancer, reducing tumor size and making surgery less invasive. ^{1 2 3 4 5}

Is nivolumab safe for use in kidney cancer treatment?

Nivolumab, used before kidney cancer surgery, appears generally safe with manageable side effects. In studies, most patients experienced mild side effects like fatigue and skin rash, while serious side effects were rare. Proper management can help reverse these side effects if they occur. ^{2 6 7 8 9}

How does the drug nivolumab with surgery differ from other treatments for kidney cancer?

Nivolumab, an immune checkpoint inhibitor, is unique because it is used before surgery (nephrectomy) to potentially shrink kidney tumors and improve surgical outcomes, which is not a common approach for localized kidney cancer. This combination aims to enhance the body's immune response against cancer cells, offering a novel strategy compared to traditional treatments that typically involve surgery alone. ^{1 2 3 4 10}

What is the purpose of this trial?

This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with nivolumab to the usual approach of nephrectomy followed by standard post-operative follow-up and monitoring, in treating patients with kidney cancer that is limited to a certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent the cancer from returning. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.

Research Team

Lauren Harshman

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Adults with localized kidney cancer (stage T2 or higher, without distant metastases) who are planning to have a kidney removed and haven't had prior cancer treatments. Participants should not have serious illnesses, active infections needing IV antibiotics, HIV, or be on high-dose steroids. They must not be pregnant/breastfeeding and agree to use contraception.

Inclusion Criteria

Patient must not have any known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results

Patient must not be currently enrolled in other clinical trials testing a therapeutic intervention

I am scheduled for kidney surgery due to a large tumor or one that has spread to lymph nodes.

Exclusion Criteria

A non-diagnostic biopsy is considered a good faith effort and does not need to be repeated unless deemed clinically necessary by the treating investigator

I have not been treated with specific immune system targeting drugs.

I had surgery or thermal ablation for a kidney tumor smaller than 3 cm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab intravenously and undergo partial or radical nephrectomy

Approximately 20 weeks

Every 14 days for 2 cycles, then every 14 days for 6 cycles, and every 28 days for 6 cycles

Follow-up

Participants are monitored for recurrence-free survival and overall survival

5 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

Treatment Details

Interventions

• Nephrectomy
• Nivolumab

Trial Overview The trial is testing if adding the drug Nivolumab after removing part or all of a kidney can prevent cancer from returning better than just surgery alone. Nivolumab boosts the immune system's ability to fight remaining cancer cells post-surgery.

Participant Groups

Group I: Arm A (nivolumab + nephrectomy) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (nephrectomy only) Active Control 4 Interventions

Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Findings from Research

A 65-year-old man with advanced renal cell carcinoma achieved a remarkable reduction in metastasis after receiving nivolumab as the fifth systemic therapy, following treatment with angiogenesis inhibitors and interferon-α.

The patient experienced a pathological complete response, with no cancer cells found after adrenalectomy, and remains healthy 20 months post-surgery, highlighting the potential efficacy of nivolumab in advanced renal cell carcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. Hagimoto, H., Kashima, S., Doi, K., et al.[2022]

In a study of 41 patients with metastatic renal cell carcinoma treated with nivolumab and ipilimumab, deferred cytoreductive nephrectomy led to significant tumor shrinkage in both primary kidney and metastatic lesions, with 86% of patients showing at least 30% reduction.

Patients who underwent deferred nephrectomy had a higher overall survival rate (100% at 1 year) compared to those who had upfront nephrectomy (72.4%) or no nephrectomy (58.2%), suggesting a potential therapeutic benefit of this approach after immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Yoshino, M., Ishihara, H., Nemoto, Y., et al.[2022]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

Nivolumab is the first PD-1 receptor inhibitor approved for treating metastasized renal cell carcinoma, requiring careful monitoring for side effects due to its immunotherapy nature.

While serious side effects (grades 3 or 4) are rare, they can affect various organs and may require treatment adjustments; however, with timely recognition and management, these immune-mediated side effects are generally reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition]. Oppel-Heuchel, H., Grimm, MO.[2018]

In a study of 91 patients with metastatic renal cell carcinoma (mRCC), nivolumab showed significant improvements in overall survival, with a median survival of 25.2 months for the highest dose (10 mg/kg) and not reached for treatment-naïve patients.

Nivolumab treatment led to substantial increases in tumor-associated lymphocytes and changes in chemokine levels, indicating its immunomodulatory effects, while no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Choueiri, TK., Fishman, MN., Escudier, B., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II Study of Neoadjuvant Nivolumab in Patients with Locally Advanced Clear Cell Renal Cell Carcinoma Undergoing Nephrectomy. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

Case of complete response to neoadjuvant therapy using nivolumab in a patient with metastatic renal cell carcinoma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

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

Outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma: a real-world multi-institution data with a minimum of 2 years of follow-up. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab in Patients with High-risk Nonmetastatic Renal Cell Carcinoma. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of nivolumab for Japanese patients with metastatic renal cell cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition]. [2018]

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

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. [2022]