Immunotherapy + Targeted Therapy for Genitourinary Cancers
Recruiting in Palo Alto (17 mi)
+318 other locations
Overseen ByAndrea B Apolo
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab 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. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot take certain medications like warfarin and strong CYP3A4 inducers or inhibitors. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What data supports the effectiveness of the drug combination of Cabozantinib, Ipilimumab, and Nivolumab for genitourinary cancers?
Research shows that combining Cabozantinib and Nivolumab, with or without Ipilimumab, has been effective in treating advanced genitourinary cancers, including urothelial carcinoma. These drugs work by boosting the immune system to fight cancer, and they have shown promising results in improving patient outcomes.
12345Is the combination of cabozantinib, nivolumab, and ipilimumab safe for humans?
Research shows that the combination of cabozantinib, nivolumab, and ipilimumab has been studied for safety in various cancers, including genitourinary tumors and renal cell carcinoma. While specific safety details are not provided, these studies indicate that the treatment has been evaluated for safety in humans.
16789How is the drug combination of Cabozantinib, Ipilimumab, and Nivolumab unique for genitourinary cancers?
This drug combination is unique because it combines targeted therapy (Cabozantinib) with immunotherapy (Nivolumab and Ipilimumab), aiming to enhance the immune system's ability to fight cancer while also targeting specific cancer cell pathways. This approach is being explored for its potential to improve outcomes in genitourinary cancers, where traditional immunotherapy alone has shown limited success.
14101112Eligibility Criteria
This trial is for adults with rare genitourinary tumors that have spread, who can swallow pills and don't have active brain metastases or certain illnesses. They may have had up to two cancer treatments before or none at all. Participants must not be on warfarin, have a good performance status (Karnofsky >=80%), no recent major surgeries, no severe allergies to monoclonal antibodies, and controlled medical conditions are okay.Inclusion Criteria
My cancer's type and stage have been confirmed with a biopsy.
My cancer has not spread to major blood vessels or the digestive system.
I do not have any active cancer spread to my brain.
I am 18 years old or older.
I am not taking warfarin or certain long-term medications.
I am mostly self-sufficient and active.
I do not have an active autoimmune disease or a history of one that might come back.
My cancer has spread to new areas or worsened, as shown on scans.
Exclusion Criteria
I have had an organ or stem cell transplant.
I have or had an autoimmune disease that could come back.
Participant Groups
The study tests how well the combination of cabozantinib (a drug blocking enzymes needed for cell growth), nivolumab and ipilimumab (both immunotherapy drugs) works against advanced genitourinary cancers compared to each drug alone. It's a phase II trial where these drugs' effectiveness in stopping tumor growth will be observed using scans like PET, CT, MRI.
1Treatment groups
Experimental Treatment
Group I: Treatment (cabozantinib, nivolumab, ipilimumab)Experimental Treatment9 Interventions
Patients receive cabozantinib PO QD on days 1-21 of cycles 1-4 and on days 1-28 of subsequent cycles. Patients also receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Patients then receive nivolumab IV over 30 minutes on day 1 of subsequent cycles. Treatment repeats every 21 days for cycles 1-4 and every 28 days for subsequent cycles for 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo echocardiography during screening and undergo CT or MRI, bone scan and blood and urine sample collection throughout the trial and may undergo PET/CT throughout the trial.
Cabozantinib S-malate is already approved in United States, United States, European Union for the following indications:
🇺🇸 Approved in United States as Cabometyx for:
- Advanced renal cell carcinoma (RCC)
- Hepatocellular carcinoma (HCC)
- Locally advanced or metastatic differentiated thyroid cancer (DTC)
🇺🇸 Approved in United States as Cometriq for:
- Medullary thyroid cancer
🇪🇺 Approved in European Union as Cabometyx for:
- Advanced renal cell carcinoma (RCC)
- Hepatocellular carcinoma (HCC)
- Locally advanced or metastatic differentiated thyroid cancer (DTC)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of Michigan Health - Sparrow LansingLansing, MI
Riverside Methodist HospitalColumbus, OH
Marshfield Medical Center-MarshfieldMarshfield, WI
HaysMedHays, KS
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. [2023]We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances.
[Mode of action, new targets and potential biomarkers in modern immunotherapy]. [2019]Immune checkpoint inhibitors (ICI) have significantly improved the systemic therapy of metastatic disease in genitourinary malignancies. With the European Medicines Agency (EMA) approval of the antibodies nivolumab and pembrolizumab directed against programmed cell death 1 (PD-1) as well as the PD-L1 antibody atezolizumab, three agents are available for the treatment of metastatic urothelial carcinoma and renal cell carcinoma. This article describes the underlying mode of action of PD-1/PD-L1 blockade and other ICIs to activate the immune system for effective tumor rejection. Future therapeutic strategies are focusing on the combination of ICI with targeted therapies to enhance the immune defense, especially in the local tumor microenvironment. A further clinical need exists for the establishment of biomarkers to predict a therapy response under ICI, in particular for the role of the PD-L1 status. Biomarkers for predicting primary or acquired therapy resistance are also of clinical importance to enable good patient selection for ICI therapy.
Targeting the Tumor Microenvironment with Immunotherapy for Genitourinary Malignancies. [2019]Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis. Despite this success, many patients fail to respond to immune checkpoint inhibitors and progression/relapse remains common. Furthermore, modest clinical activity has been observed with ICIs as a monotherapy in advanced PCa. As such, novel treatment approaches are warranted and improved biomarkers for patient selection and treatment response are desperately needed. Future efforts should focus on exploring synergistic and rational combinations that safely and effectively boost response rates and survival in genitourinary malignancies. Specific areas of interest include (1) evaluating the optimal sequencing, disease burden, and timing of immuno-oncology agents with other anti-cancer therapeutics and (2) validating novel biomarkers of response to immunotherapy to optimize patient selection and to identify individuals most likely to benefit from immunotherapy across the heterogenous spectrum of genitourinary malignancies.
Updated EAU Guidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy. [2018]The European Association of Urology renal cancer guidelines have been updated to recommend nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of VEGF targeted therapy.
Immunotherapy in Genitourinary Malignancy: Evolution in Revolution or Revolution in Evolution. [2022]Immunotherapy, the 5th pillar of cancer care after surgery, radiotherapy, cytotoxic chemotherapy, and precision therapy (molecular targeted therapy), is revolutionizing the standard of care in certain patients with genitourinary malignancies. As modest clinical benefits of IL-2 for metastatic renal cell carcinoma and Bacillus Calmette-Guerin therapy for early-stage bladder cancers in the past years, immune checkpoint inhibitors therapies demonstrate meaningful survival benefit and durable clinical response in renal cell carcinoma, urothelial carcinoma, and some prostate cancer. Despite best efforts, the benefits are limited to a minority of unselected patients due to the complexities of biomarker development. Now come the next hurdles: figuring out which patients best respond to immune checkpoint inhibitors and which patients won't respond to immune checkpoint inhibitors? How best to approach immune checkpoint inhibitors therapies to extend/maximize the treatment response as long as possible? How to overcome therapeutic resistance by specific concurrent immunomodulators or targeted therapy or chemotherapy? The role of immune checkpoint inhibitors in combination or sequencing with chemotherapy or other targeted therapies or other immunomodulating therapeutics in the early disease, neoadjuvant, adjuvant, and metastatic setting is actively under exploration. Ideal strategy for cancer care is to provide not just more time, but more quality time: there remain unmet needs for novel therapies that exploit molecular or genetic pathways to extend survival without compromising health-related quality of life for patients with advanced genitourinary malignancies. Further research is needed to discover new therapeutic strategies, and validate efficacy and effectiveness in real-world settings.
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]Recently, many agents and combinations for metastatic and advanced renal cell carcinoma have been approved. This study aims to highlight the comprehensive differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) and ipilimumab (IPI) plus NIVO based on a real-world big dataset.
Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). [2022]Patients with metastatic castration-resistant prostate cancer have few treatment options after novel hormonal therapy (eg, abiraterone or enzalutamide). We aimed to evaluate cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, in combination with the PD-L1 inhibitor atezolizumab in metastatic castration-resistant prostate cancer.
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non-clear-cell renal cell carcinoma (RCC).
Blocking immune checkpoints in prostate, kidney, and urothelial cancer: An overview. [2023]Despite a long history of immunotherapeutic approaches to treatment, most genitourinary malignancies are not cured by existing immunotherapy regimens. More recently, cell surface molecules known as immune checkpoints have become the focus of efforts to develop more effective immunotherapies. Interactions between these molecules and their ligands inhibit the proliferation and function of tumor-specific lymphocytes. A monoclonal antibody blocking 1 of these checkpoints was approved for the treatment of metastatic melanoma and is now being tested in other malignancies. The objective responses seen in these early trials of checkpoint blockade are driving renewed enthusiasm for cancer immunotherapy. There are several ongoing and planned trials in genitourinary malignancies of single-agent inhibitors, as well as combinations targeting multiple checkpoints or adding other types of therapies to checkpoint blockade.
The immune infiltrate in prostate, bladder and testicular tumors: An old friend for new challenges. [2017]In genito-urinary tumors immunotherapy has been administered for a long time: Calmette-Guèrin Bacillus as adjuvant treatment in high risk patients with non muscle invasive urothelial bladder cancer and interleukin-2 and interferon-α in metastatic kidney cancer. The vaccine Sipuleucel-T has been approved by United States Food and Drug Administration for the treatment of castration resistant prostate cancer patients with asymptomatic or minimally symptomatic disease, given the 22% reduction of mortality risk in this group. Recently immunotherapeutic agents targeting inhibitory immune checkpoint molecules lead to improved outcomes and lasting anti-tumor effects in a variety of hematological and solid malignancies, including urogenital tumors. The benefit from these treatments has been observed only in a proportion of subjects, raising a need in optimizing patients' selection for immune checkpoint blockade. The composition and activity of a pre-existing immune infiltrate may aid in identifying ideal candidates to immunotherapy, with possible implications for the clinical management of neoplastic diseases from earlier to later stages.
The immunotherapy revolution in genitourinary malignancies. [2021]Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with renal cell cancer, prostate cancer and bladder cancer, with limited responses in testicular cancer. The role of immunotherapy in combination with chemotherapy or other targeted therapies in the neo-adjuvant, adjuvant and metastatic setting is actively being explored. We describe the current immunotherapy-related treatment modalities approved for genitourinary cancers, focusing on immune checkpoint inhibitors, vaccines and other modalities, and highlight ongoing studies involving immunotherapy in these cancer types.