Immunotherapy for Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV/AIDS, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

Duration: 6 weeks

104 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized pilot early phase I trial studies the side effects and how well nivolumab alone works compared to nivolumab with bevacizumab or ipilimumab before surgery in treating patients with kidney cancer, also referred to as renal cell cancer, that has spread to another place in body and can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, bevacizumab, and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, patients on high-dose steroids or other potent immune suppression medications, as well as those requiring ongoing anticoagulation (except aspirin), are excluded. It's best to discuss your specific medications with the trial team.

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

Research shows that Nivolumab, a drug that helps the immune system fight cancer, improved survival in patients with advanced kidney cancer compared to another treatment called everolimus. ^{1 2 3 4 5}

What safety data exists for immunotherapy treatments like Nivolumab and Ipilimumab in kidney cancer?

Immunotherapy treatments like Nivolumab and Ipilimumab can cause immune-related side effects, which may affect various organs. Common side effects include inflammation of the colon, liver, skin, and thyroid, while rare but serious effects can include heart and lung inflammation. These treatments have been studied in kidney cancer and other conditions, showing a need for careful monitoring of these side effects. ^{6 7 8 9 10}

How is the drug Nivolumab unique in treating kidney cancer?

Nivolumab is unique because it is an immune checkpoint inhibitor that helps the body's immune system attack cancer cells, specifically targeting the PD-1 pathway. It has shown a survival advantage in patients with advanced kidney cancer who have already received other treatments, offering a new option after anti-angiogenic therapy. ^{4 11 12 13 14}

Research Team

Padmanee Sharma, MD, PhD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with metastatic clear cell renal cell carcinoma (kidney cancer) that can be surgically removed. Participants must understand the study and risks, may have had previous treatments except certain immunotherapies or bevacizumab, and should meet specific health criteria like adequate blood counts and organ function.

Inclusion Criteria

My kidney cancer has spread, and I am eligible for surgery to remove the tumor.

I have a tumor or lymph node that can be measured and meets the size requirements.

I have had treatments for kidney cancer but not with PD1 or CTLA-4 inhibitors or bevacizumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab alone or in combination with bevacizumab or ipilimumab for 6 weeks, followed by surgery

6 weeks

3 visits (in-person)

Surgery

Patients undergo nephrectomy, metastasectomy, or biopsy approximately 4 weeks after treatment

1 day

1 visit (in-person)

Maintenance Therapy

Patients receive maintenance nivolumab every 4 weeks for up to 2 years if they have a clinical response or stable disease

Up to 2 years

Every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

30 days, 86 days, every 3 months for 2 years, every 6 months for 1 year, then annually

Treatment Details

Interventions

• Bevacizumab
• Ipilimumab
• Nivolumab

Trial Overview The trial tests how well nivolumab works alone or combined with bevacizumab or ipilimumab before surgery in patients with kidney cancer. It's an early phase I pilot study to see if these monoclonal antibodies can boost the immune system to fight cancer and prevent tumor growth.

Participant Groups

Group I: Arm C (nivolumab, ipilimumab, surgery) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1 every 3 weeks for 6 weeks. Patients also undergo nephrectomy, metastasectomy or biopsy as in Arm A. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (nivolumab, bevacizumab, surgery) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 60 minutes and bevacizumab IV over 90 minutes on day 1 every 2 weeks for 6 weeks. Patients also undergo nephrectomy, metastasectomy or biopsy as in Arm A. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group III: Arm A (nivolumab, surgery) Experimental Treatment 5 Interventions

Patients receive nivolumab IV over 60 minutes on day 1 every 2 weeks for 6 weeks. Approximately 4 weeks later, patients undergo nephrectomy, metastasectomy or biopsy. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Nivolumab, an anti-PD-1 antibody, shows promising effects in the treatment of advanced renal cancer, indicating its potential as an effective immunotherapy option.

The manuscript highlights the role of nivolumab in harnessing the immune system to target and combat renal cancer, suggesting a new avenue for treatment in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer]. Ozono, S.[2018]

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]

Nivolumab, an immune-checkpoint inhibitor used to treat lung adenocarcinoma, can lead to autoimmune side effects, as demonstrated by a case of acute tubulointerstitial nephritis in a 67-year-old patient after three infusions.

The kidney biopsy revealed specific histological changes, including proliferation of certain immune cells, indicating that nivolumab can trigger significant immune responses that may affect organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. Uchida, A., Watanabe, M., Nawata, A., et al.[2021]

In a study of 69 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival (OS) and progression-free survival compared to those without irAEs, suggesting that irAEs may be a positive indicator of treatment response.

The study identified three key factors influencing OS: the presence of irAEs, C-reactive protein levels, and performance status, indicating that monitoring these factors could help predict patient outcomes in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. Nukaya, T., Takahara, K., Yoshizawa, A., et al.[2023]

In a study of 53 patients with metastatic renal cell carcinoma treated with nivolumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival compared to those without irAEs, indicating a potential link between irAEs and treatment efficacy.

The study found that a lower platelet-to-lymphocyte ratio before treatment was a risk factor associated with the development of irAEs, suggesting that this ratio could be a useful predictor for monitoring patient responses to nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. Kobayashi, K., Iikura, Y., Hiraide, M., et al.[2021]

This case report describes the first known instance of minimal change disease with nephrotic syndrome linked to the PD-1 inhibitor Nivolumab, occurring in a 57-year-old man after one month of treatment for metastatic squamous cell carcinoma.

Despite treatment with corticosteroids and stopping Nivolumab, the patient's kidney function and nephrotic syndrome did not improve, highlighting the need for awareness of various kidney complications associated with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal change disease in a patient receiving checkpoint inhibition: Another possible manifestation of kidney autoimmunity? Vaughan, E., Connolly, E., Hui, M., et al.[2021]

Nivolumab showed antitumor activity in patients with metastatic renal cell carcinoma (mRCC), with median overall survival rates of 18.2, 25.5, and 24.7 months across three different doses, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with fatigue being the most common side effect; however, no significant dose-response relationship was found in terms of progression-free survival, suggesting that the efficacy may not increase with higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. Motzer, RJ., Rini, BI., McDermott, DF., et al.[2022]

Nivolumab (Opdivo®) has been established as an effective second-line treatment for metastatic renal cell carcinoma (mRCC), showing improved overall survival (26 months vs. 19.7 months) and response rates compared to Everolimus, based on the CheckMate 025 trial with 1,080 participants.

The combination of Nivolumab and Ipilimumab has demonstrated a significantly higher objective response rate (42% vs. 27%) and better overall survival in intermediate and high-risk patients compared to Sunitinib, while also improving quality of life, despite an increase in immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for renal cell carcinoma - current status]. Grimm, MO., Foller, S.[2019]

References

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

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

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

Nivolumab drug holiday in patients treated for metastatic renal cell carcinoma: A real-world, single-centre experience. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer]. [2018]

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

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

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

6. Japan pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. [2021]

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

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. [2021]

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

Minimal change disease in a patient receiving checkpoint inhibition: Another possible manifestation of kidney autoimmunity? [2021]

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

Immune Related Adverse Events: Classification and Management Approaches in Advanced Kidney Cancer. [2021]

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

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. [2022]

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

FDA Approval Summary: Nivolumab in Advanced Renal Cell Carcinoma After Anti-Angiogenic Therapy and Exploratory Predictive Biomarker Analysis. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of advanced renal cell carcinoma. [2018]

14. Germany pubmed.ncbi.nlm.nih.gov

[Immunotherapy for renal cell carcinoma - current status]. [2019]