Nivolumab + Ipilimumab With/Without Camu Camu for Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Nivolumab, Ipilimumab

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Brain metastases, Autoimmune disease, 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

Compensation: Varies

Number of Visits: 15

Duration: 12 weeks for initial cycles, then ongoing every 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for advanced kidney cancer that has spread. Researchers are testing the safety and optimal dose of camu camu, a prebiotic that might boost the immune system, when combined with two existing cancer drugs, nivolumab and ipilimumab, which help the immune system fight cancer. Participants will receive either the standard treatment with nivolumab and ipilimumab or the new combination that includes camu camu. Those with kidney cancer that cannot be treated with surgery or radiation and whose cancer has spread may be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use probiotics, prebiotics, yogurt, bacterial fortified foods, and other natural supplements within 2 weeks before and during the treatment period.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using nivolumab and ipilimumab together in patients with advanced kidney cancer yields promising safety results. In other studies, patients experienced manageable side effects, and the treatment was generally safe. For instance, 7% of patients had liver inflammation caused by the immune system, but severe cases were rare.

Now, consider the trial with these two drugs plus an extra ingredient—camu camu. This combination remains in the early testing phase, so complete safety information is not yet available. However, since nivolumab and ipilimumab are already approved for kidney cancer, they are considered safe for patients.

This trial aims to find the best dose and understand any side effects when camu camu is added. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for kidney cancer, which often involve combinations of immunotherapy drugs like nivolumab and ipilimumab, this new approach adds camu camu, a fruit known for its high vitamin C content, as a potential game-changer. Researchers are excited because camu camu might enhance the immune response, offering a novel way to boost the effectiveness of existing immunotherapies. This could provide a more robust defense against cancer cells, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research has shown that using nivolumab and ipilimumab together, which participants in this trial may receive, effectively treats advanced kidney cancer. Studies indicate that this treatment can lower the risk of death by up to 37% compared to sunitinib, another cancer drug. Additionally, more than half of the patients receiving this combination have experienced significant survival benefits.

In this trial, another group of participants will receive a combination of nivolumab, ipilimumab, and camu camu. Early findings suggest that adding camu camu might boost the immune system's ability to fight cancer. Initial studies found that this combination reduced tumor size more effectively than nivolumab and ipilimumab alone. This suggests that camu camu could potentially improve treatment outcomes for metastatic kidney cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Sumanta K. Pal

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer that has spread. Participants must have adequate kidney and liver function, no prior treatments targeting PD-1 or PD-L1, and not be on immunosuppressants. They should not have favorable risk disease by IMDC classification, active autoimmune diseases, severe lung issues, recent heart problems, untreated brain metastases or be pregnant.

Inclusion Criteria

You have a cancer that can be measured using specific criteria called RECIST 1.1.

My kidney cancer is classified as intermediate or poor risk.

My liver is functioning well according to recent tests.

Exclusion Criteria

Your white blood cell count is less than 2,000 per cubic millimeter.

Your neutrophil count is less than 1,500 per cubic millimeter.

My kidney cancer is considered low risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab and ipilimumab with or without camu camu. Cycles repeat every 3 weeks for cycles 1-4, then every 4 weeks starting cycle 5.

12 weeks for initial cycles, then ongoing every 4 weeks

Visits every 3 weeks for cycles 1-4, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 12 weeks.

Every 12 weeks until death or withdrawal

Follow-up visits every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Camu Camu
• Ipilimumab
• Nivolumab

Trial Overview The trial tests the safety and optimal dose of camu camu combined with nivolumab and ipilimumab in metastatic renal cell carcinoma. It explores whether this prebiotic supplement can enhance the effectiveness of these monoclonal antibodies which boost the immune system's response to cancer.

How Is the Trial Designed?

Group I: Arm 2 (nivolumab, ipilimumab, camu camu) Experimental Treatment 7 Interventions

Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.

Group II: Arm 1 (nivolumab and ipilimumab) Active Control 6 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.

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

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A 73-year-old hemodialysis patient with metastatic renal cell carcinoma was treated with the combination of ipilimumab and nivolumab, which was administered safely without any adverse events.

This case suggests that ipilimumab-nivolumab can be a viable treatment option for metastatic renal cell carcinoma in patients on hemodialysis, a group that typically has limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. Iwaki, T., Niimi, A., Kano, M., et al.[2022]

In a phase 3 trial involving 1096 patients with untreated advanced renal-cell carcinoma, nivolumab plus ipilimumab significantly improved overall survival rates (75% at 18 months) compared to sunitinib (60% at 18 months), indicating a more effective treatment option for patients with intermediate or poor prognostic risk.

The objective response rate was also higher with nivolumab plus ipilimumab (42%) compared to sunitinib (27%), although both treatments had a high incidence of treatment-related adverse events, with nivolumab plus ipilimumab showing a slightly lower rate of severe (grade 3 or 4) events (46% vs. 63%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. Motzer, RJ., Tannir, NM., McDermott, DF., et al.[2022]

In a study of 46 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, 72% experienced immune-related adverse events (irAEs), which were linked to significantly longer progression-free survival (PFS) compared to those without irAEs.

While irAE development was an independent predictor of longer PFS, it did not affect overall survival (OS), suggesting that irAEs could serve as a useful prognostic marker for treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Ikeda, T., 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]

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]

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]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

A 60-year-old man with intermediate prognosis renal cell carcinoma achieved a complete pathological response after receiving ipilimumab and nivolumab combination therapy, highlighting the efficacy of this treatment approach in metastatic cases.

The treatment was associated with immune-related side effects, such as hypophysitis and oligoarthritis, which occurred more than a year after starting therapy, indicating the need for ongoing monitoring for potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pathological Complete Response to the Combination of Ipilimumab and Nivolumab in a Patient with Metastatic Renal Cell Carcinoma. Studentova, H., Zemankova, A., Spisarova, M., et al.[2022]

The combination of nivolumab and ipilimumab is an effective treatment for metastatic renal cell carcinoma (mRCC), showing a pathologic complete response in a patient with a large tumor and lymphadenopathy.

This case highlights the potential for durable responses with minimal toxicity from this combination therapy, suggesting it may be a promising option for patients classified as intermediate-risk mRCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic Complete Response to Neoadjuvant Nivolumab/Ipilimumab in a Patient with Metastatic Renal Cell Carcinoma. Peak, TC., Fenu, EM., Rothberg, MB., et al.[2020]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

In a study of 52 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, the 1-year progression-free survival rate was 55% and the overall survival rate was 75%, indicating promising efficacy of this treatment combination.

The treatment was associated with a 39% objective response rate, and while 69% of patients experienced immune-related adverse events, the incidence of severe events was lower compared to previous studies, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study. Tanaka, T., Hatakeyama, S., Numakura, K., et al.[2021]

In a pooled analysis of 410 patients with advanced clear cell renal cell carcinoma, nivolumab plus ipilimumab showed a modest objective response rate of 12.6% in patients who did not respond to prior nivolumab treatment, indicating that a small subset may still benefit from this combination therapy.

The study found that the overall survival rate at three years was 59%, suggesting that while the response to salvage therapy is limited, the combination can still provide significant long-term survival benefits for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma. McKay, RR., Leucht, K., Xie, W., et al.[2023]

In a real-world study of 195 patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab, the estimated median overall survival was 54.5 months, indicating a significant survival benefit similar to that seen in clinical trials.

The treatment was generally well-tolerated, but 45% of patients discontinued due to disease progression and 18% due to toxicity, with colitis being the most common adverse event, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization and Safety of Ipilimumab Plus Nivolumab in a Real-World Cohort of Metastatic Renal Cell Carcinoma Patients. Thana, M., Basappa, NS., Ghosh, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40271863/

The Effectiveness and Safety Profile of Nivolumab-Plus ... J-ENCORE is an ongoing multicenter, prospective, observational study of the effectiveness and safety of nivolumab-plus-ipilimumab for patients in Japan

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39705641/

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients ...

3. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... Patients with previously untreated advanced or metastatic renal cell carcinoma treated with Opdivo plus Yervoy experienced a 28% reduction in the risk of death ...

4. ascopubs.org ascopubs.org/doi/10.1200/CCI.24.00132

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients with I/P-risk mRCC.

5. opdivo.com opdivo.com/advanced-kidney-cancer/clinical-trial-results/immunotherapy-combination

Clinical trial results for advanced kidney cancer (renal cell ... In the clinical trial, people given OPDIVO + YERVOY had a 37% lower risk of dying than those given SUTENT, and more than half of the people given OPDIVO + ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6289271/

Ipilimumab in combination with nivolumab for the treatment of ... The combination of nivolumab and ipilimumab has demonstrated superior efficacy for treatment-naïve patients with intermediate- and poor-risk mRCC with clear ...

7. cancernetwork.com cancernetwork.com/view/nivolumab-combo-may-show-long-term-benefits-in-advanced-rcc

Nivolumab Combo May Show Long-Term Benefits in ... Combining nivolumab (Opdivo) with ipilimumab (Yervoy) may potentially improve long-term outcomes in patients with advanced renal cell carcinoma (RCC).

8. opdivohcp.com opdivohcp.com/efficacy/rcc

Efficacy Data for Renal Cell Carcinoma (RCC) - Opdivo In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), ...