Triple Drug Therapy for Kidney Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Corticosteroids, Immunosuppressives
Disqualifiers: Active infection, CNS metastasis, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To learn if the combination of ciforadenant, ipilimumab, and nivolumab can help to control advanced renal cell carcinoma
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the trial treatment.
What data supports the effectiveness of the drug combination of Ciforadenant, Ipilimumab, and Nivolumab for kidney cancer?
The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) has been shown to improve overall survival in patients with advanced renal cell carcinoma, as demonstrated in a large clinical trial. This combination is already approved for use in certain kidney cancer patients, indicating its effectiveness.
12345Is the triple drug therapy for kidney cancer safe?
The combination of nivolumab and ipilimumab, part of the triple drug therapy, can cause significant side effects, including severe immune-related reactions. These side effects are more frequent and severe when the drugs are used together, but they are often manageable with medications like glucocorticoids. Close monitoring by experienced healthcare providers is essential to manage these reactions effectively.
36789What makes the triple drug therapy for kidney cancer unique?
The triple drug therapy for kidney cancer is unique because it combines Ciforadenant with the already established combination of nivolumab (Opdivo) and ipilimumab (Yervoy), which are known to improve survival in patients with advanced renal cell carcinoma. This combination leverages the immune-boosting effects of nivolumab and ipilimumab, which are immune checkpoint inhibitors, potentially offering a novel approach by adding Ciforadenant, which may further enhance the immune response against cancer cells.
410111213Eligibility Criteria
Adults with Stage IV metastatic renal cell carcinoma who have not had prior systemic therapy for advanced RCC. Participants must have adequate organ function, be willing to use contraception, and able to provide consent. Excluded are those with recent major surgery, active autoimmune diseases, or conditions requiring immunosuppressants.Inclusion Criteria
Women who can have babies must have a negative pregnancy test within 24 hours before starting the treatment.
I have been diagnosed with clear cell renal cell carcinoma.
I have not received any systemic therapy for advanced kidney cancer.
+11 more
Exclusion Criteria
I haven't had any cancer treatment, including immune or targeted therapies, in the last 6 months.
I cannot take pills by mouth or have a severe gut problem affecting drug absorption.
I haven't had major surgery in the last 28 days.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ipilimumab, nivolumab, and ciforadenant to control advanced renal cell carcinoma
12 weeks
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Participant Groups
The trial is testing a combination of three drugs: Ciforadenant (an adenosine A2a receptor antagonist), Ipilimumab, and Nivolumab in patients with advanced renal cell carcinoma to see if this mix can control the disease better than current treatments.
1Treatment groups
Experimental Treatment
Group I: Ipilimumab, Nivolumab, and CiforadenantExperimental Treatment3 Interventions
To help control advanced renal cell carcinoma.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke Cancer InstituteDurham, NC
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, PA
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Safe and effective use of nivolumab plus ipilimumab in a patient with metastatic clear-cell renal cell carcinoma with sarcomatoid dedifferentiation and end stage renal disease on hemodialysis. [2022]Targeting the programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) pathways using the combination immune checkpoint inhibitors (ICI) nivolumab and ipilimumab is an approved frontline therapy for patients with metastatic clear-cell renal cell carcinoma (mccRCC). Certain populations pose clinical challenges due to exclusion from large clinical trials that established the safety and efficacy of these treatments, including patients with end stage renal disease (ESRD). While there are reports successfully administering single-agent ICI in patients with ESRD, we present herein a case of safe and effective use of combination nivolumab plus ipilimumab in a 53-year-old man with mccRCC with sarcomatoid dedifferentiation and ESRD on hemodialysis.
Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study. [2021]To investigate the efficacy and safety of first-line nivolumab plus ipilimumab for patients treated with metastatic renal cell carcinoma.
Two cases of anaphylaxis due to contrast media during administration of nivolumab and ipilimumab in metastatic renal cell carcinoma. [2020]A combination therapy of nivolumab and ipilimumab is effective for advanced renal cell carcinoma, but there are concerns about immune-related adverse events. A 46-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On days 16 and 49, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. A 70-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On day 44, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. Both patients were diagnosed with anaphylaxis due to the contrast agent.
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. [2021]On the 15 November 2018, the Committee for Medicinal Products for Human Use adopted an extension to an existing indication for the use of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adult patients with intermediate/poor-risk advanced renal cell carcinoma (RCC). The approval was based on results from the Pivotal CA209214 study, a randomised, open-label, phase III study, comparing nivolumab +ipilimumab with sunitinib in subjects≥18 years of age with previously untreated advanced RCC (not amenable for surgery or radiotherapy) or metastatic RCC, with a clear-cell component. A total of 1096 patients were randomised in the trial, of which 847 patients had intermediate/poor-risk RCC and received either nivolumab (n=425) in combination with ipilimumab administered every 3 weeks for 4 doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks or sunitinib (n=422) administered orally for 4 weeks followed by 2 weeks off, every cycle. A statistically significant difference in overall survival (OS) was observed in the nivolumab + ipilimumab group compared with the sunitinib group in intermediate/poor-risk subjects (HR 0.63 (99.8% CI 0.44 to 0.89); stratified log-rank 2-sided p-value
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. [2022]Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.
PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma. [2022]The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy.
Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. [2022]Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well trained to identify ADR promptly and monitor patients adequately. This paper reviews safety data assessed by the European Medicines Agency for the anti-PD-1/CTLA-4 combination and provides a literature overview on published case reports for rare ADR with suspected potential underreporting. Incidences and kinetics of immune-related ADR are described. Recommendations for the evaluation and management of ADR are convened by an interdisciplinary expert panel focusing on rare but clinically important side effects arising from combined ICB. Pooled safety data from 1551 patients with advanced melanoma, treated either with 3mg/kg ipilimumab plus 1mg/kg nivolumab (N=407), or nivolumab alone (N=787), or ipilimumab alone (N=357) demonstrate that immune-related ADR occur more frequently for the combination, with a shorter time-to-onset, and tend to be more severe. The majority of events is reversible after systemic use of glucocorticoids, notably methylprednisolone or equivalents; in certain cases of long-lasting and refractory immune toxicities, non-steroidal immunosuppressants may be used, once ICB is interrupted or terminated. Combined ICB has considerable toxicities, therefore close monitoring and high experience in diagnosis and treatment of ADR is necessary.
Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. [2021]Purpose The clinical activity observed in a phase I dose-escalation study of concurrent therapy with nivolumab (NIVO) and ipilimumab (IPI) in patients with previously treated or untreated advanced melanoma led to subsequent clinical development, including randomized trials. Here, we report long-term follow-up data from study CA209-004, including 3-year overall survival (OS). Patients and Methods Concurrent cohorts 1, 2, 2a, and 3 received escalating doses of NIVO plus IPI once every 3 weeks for four doses, followed by NIVO once every 3 weeks for four doses, then NIVO plus IPI once every 12 weeks for eight doses. An expansion cohort (cohort 8) received concurrent NIVO 1 mg/kg plus IPI 3 mg/kg once every 3 weeks for four doses, followed by NIVO 3 mg/kg once every 2 weeks, which is the dose and schedule used in phase II and III studies and now approved for patients with unresectable or metastatic melanoma. Results Among all concurrent cohorts (N = 94) at a follow-up of 30.3 to 55.0 months, the 3-year OS rate was 63% and median OS had not been reached. Objective response rate by modified WHO criteria was 42%, and median duration of response was 22.3 months. Incidence of grade 3 and 4 treatment-related adverse events was 59%. The most common grade 3 and 4 treatment-related adverse events were increases in lipase (15%), alanine aminotransferase (12%), and aspartate aminotransferase (11%). One treatment-related death (1.1%) occurred in a patient who had multiorgan failure 70 days after the last dose of NIVO plus IPI. Conclusion This is the longest follow-up for NIVO plus IPI combination therapy in patients with advanced melanoma. The 3-year OS rate of 63% is the highest observed for this patient population and provides additional evidence for the durable clinical activity of immune checkpoint inhibitors in the treatment of advanced melanoma.
Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]Combined immune checkpoint blockade with nivolumab and ipilimumab is standard therapy for the treatment of patients with previously untreated advanced renal cell carcinoma who are at intermediate or poor risk. However, data about the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in patients on hemodialysis are limited. Renal function has no known clinically important effects on the pharmacokinetics and clearance of nivolumab and ipilimumab. Further, most immune-related adverse events in patients on hemodialysis are thought to be manageable with the same treatments applied in patients with normal renal function. We present a case of advanced clear-cell renal cell carcinoma in a patient on hemodialysis who received combined immune checkpoint blockade with nivolumab and ipilimumab and who showed no evident signs of immune-related adverse events. Here, we confirm the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in a patient on hemodialysis.
Immunochemotherapy for metastatic renal cell carcinoma using a regimen of interleukin-2, interferon-alpha and 5-fluorouracil. [2013]Promising results of recent clinical trials with a triple drug bio-chemotherapy regimen encouraged its use in patients with renal cell carcinoma.
Updates to the Management of Kidney Cancer. [2019]Several updates were made to the 2018 NCCN Guidelines for Kidney Cancer. Adjuvant sunitinib is the first adjuvant therapy to be endorsed by the panel for patients with stage II and III clear cell histology renal cell carcinoma (RCC; category 2B). A promising new treatment-ipilimumab plus nivolumab for patients at intermediate and poor risk in the frontline setting-was added to the guidelines as well. Cabozantinib was added as a first-line option for poor- and intermediate-risk patients with advanced RCC.
[Second and further lines treatment options for locally advanced or metastatic renal cell carcinoma]. [2023]The treatment of locally advanced, inoperable or metastatic kidney tumors is a dynamically changing field of oncology. Since the registration of the first targeted therapeutic product (2005), more and more new products have been internationally accepted and registered almost every year. The development of immune checkpoint inhibitors and their inclusion in care algorithms (2015) further expanded the therapeutic possibilities. Despite all this, the optimal selection of medication used in different therapeutic lines poses a significant challenge to clinicians. In this review we have collected the data, aspects, and results of clinical tests necessary for the choice of therapy that can be applied in second and further lines. We also present the domestic treatment options.
Interferon-alpha plus capecitabine and thalidomide in patients with metastatic renal cell carcinoma: a pilot study. [2022]To assess the activity and toxicity of interferon-alpha (IFN-alpha), capecitabine, and thalidomide in patients with metastatic renal cell carcinoma (MRCC).