Axitinib + Nivolumab for Melanoma
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Corticosteroids, Immunosuppressives
Disqualifiers: Autoimmune disease, Cardiovascular disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The researchers are doing this study to find out whether the combination of axitinib and nivolumab is an effective and safe treatment for people with advanced or metastatic mucosal melanoma that has not been treated before.
The researchers think that a combination of axitinib and nivolumab may help people with this disease because both drugs target and block proteins that play a role in cancer cell survival and growth. The researchers think the drugs may be more effective if given in combination rather than on their own.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic treatments like corticosteroids or immunosuppressive medications, you may need to stop them 14 days before starting the trial drugs.
What data supports the effectiveness of the drug combination Axitinib and Nivolumab for treating melanoma?
Research shows that Nivolumab, a part of the combination, has demonstrated long-term survival benefits for advanced melanoma patients. Additionally, combining Nivolumab with another drug, Ipilimumab, has shown significant improvements in patient response and survival compared to using Ipilimumab alone.
12345What safety information is available for the combination of Axitinib and Nivolumab in treating melanoma?
Nivolumab, used alone or in combination with other drugs, has been associated with side effects like fatigue, diarrhea, and skin reactions such as psoriasis. When combined with other treatments, it may increase the risk of immune-related side effects, but more studies are needed to fully understand its safety profile.
678910How is the drug combination of Axitinib and Nivolumab unique for treating melanoma?
The combination of Axitinib and Nivolumab for melanoma is unique because it pairs a targeted therapy (Axitinib, which inhibits blood vessel growth in tumors) with an immune checkpoint inhibitor (Nivolumab, which helps the immune system attack cancer cells), potentially offering a novel approach compared to existing treatments that often use either type of drug alone.
123511Eligibility Criteria
Adults with advanced mucosal melanoma that hasn't been treated before can join this trial. They should have a certain type of tumor, be in good enough health to perform daily activities (ECOG 0-2), and not be pregnant or breastfeeding. Participants must agree to use two contraception methods if applicable. People with severe allergies to the drugs, autoimmune diseases needing steroids, recent heart issues, or specific blood disorders cannot join.Inclusion Criteria
I am 18 years old or older.
My melanoma cannot be removed by surgery and started in specific areas like the mouth, nose, or genitals.
I have not had any systemic therapy for my condition before joining this study.
+5 more
Exclusion Criteria
I have had heart issues within a specific timeframe.
I don't have current bleeding issues or recent serious blood clots.
I am currently receiving treatment for another cancer.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive nivolumab IV 480mg every 4 weeks plus axitinib 5mg twice daily. Upon progression, SBRT or ipilimumab may be added.
104 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Extension
Participants may continue treatment with nivolumab and axitinib if they show good tolerance and progression
Long-term
Participant Groups
The study is testing whether axitinib combined with nivolumab is effective for treating advanced mucosal melanoma. Axitinib blocks cancer cell growth signals while nivolumab boosts the immune system's response against cancer cells. The hope is that together they work better than alone.
1Treatment groups
Experimental Treatment
Group I: Axitinib and Nivolumab for the Treatment of Mucosal MelanomaExperimental Treatment3 Interventions
This is a single center trial enrolling up to 20 total evaluable patients with unresectable primary or advanced mucosal melanomas arising from the head and neck, gastrointestinal, or genitourinary tract to receive frontline therapy with nivolumab IV 480mg q4 weeks plus axitinib 5mg PO twice daily. A Simon 2-stage design will be utilized. Upon progression with good tolerance, addition of stereotactive body radiation therapy (SBRT) or CTLA-4 blockade to continued nivolumab plus axitinib will be offered to patients depending on the type of progression. For patients with local or oligometastatic progression, stereotactic body radiotherapy (SBRT) will be added; for patients with progression in a site of prior radiotherapy or with multifocal or distant progression not amenable to SBRT, ipilimumab 1mg/kg IV q3 weeks for up to 4 doses will be added.
Axitinib is already approved in European Union, United States, United Kingdom for the following indications:
🇪🇺 Approved in European Union as Inlyta for:
- Renal cell carcinoma
🇺🇸 Approved in United States as Inlyta for:
- Advanced renal cell carcinoma
🇬🇧 Approved in United Kingdom as Inlyta for:
- Advanced renal cell carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
Memorial Sloan Kettering WestchesterHarrison, NY
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
PfizerIndustry Sponsor
References
The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients.
Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]Nivolumab plus ipilimumab achieves higher response rates than previously reported for nivolumab alone.
Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study. [2022]To assess efficacy and toxicity of combination immunotherapy with ipilimumab plus nivolumab in routine practice in a retrospective multicentre cohort of patients with advanced melanoma.
Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. [2022]Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma.
Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. [2018]Nivolumab is an anti-PD1 checkpoint inhibitor active in patients with advanced melanoma and as adjuvant therapy in high-risk metastatic melanoma patients.
FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]On November 23, 2015, the FDA approved nivolumab (OPDIVO; Bristol-Myers Squibb) as a single agent for the first-line treatment of patients with BRAFV600 wild-type, unresectable or metastatic melanoma. An international, double-blind, randomized (1:1) trial conducted outside of the United States allocated 418 patients to receive nivolumab 3 mg/kg intravenously every 2 weeks (n = 210) or dacarbazine 1,000 mg/m2 intravenously every 3 weeks (n = 208). Patients with disease progression who met protocol-specified criteria (∼25% of each trial arm) were permitted to continue with the assigned treatment in a blinded fashion until further disease progression is documented. Overall survival was statistically significantly improved in the nivolumab arm compared with the dacarbazine arm [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.30-0.60; P < 0.0001]. Progression-free survival was also statistically significantly improved in the nivolumab arm (HR, 0.43; 95% CI, 0.34-0.56; P < 0.0001). The most common adverse reactions (≥20%) of nivolumab were fatigue, diarrhea, constipation, nausea, musculoskeletal pain, rash, and pruritus. Nivolumab demonstrated a favorable benefit-risk profile compared with dacarbazine, supporting regular approval; however, it remains unclear whether treatment beyond disease progression contributes to the overall clinical benefit of nivolumab. Clin Cancer Res; 23(14); 3479-83. ©2017 AACR.
Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]Recent studies suggest that combining nivolumab with ipilimumab is a more effective treatment for melanoma patients, compared to using ipilimumab or nivolumab alone. However, treatment with these immunotherapeutic agents is frequently associated with increased risk of toxicity, and (auto-) immune-related adverse events. The precise pathophysiologic mechanisms of these events are not yet clear, and evidence from clinical trials and translational studies remains limited. Our retrospective analysis of ~7700 metastatic melanoma patients treated with ipilimumab and/or nivolumab from the FDA Adverse Event Reporting System (FAERS) demonstrates that the identified immune-related reactions are specific to ipilimumab and/or nivolumab, and that when the two agents are administered together, their safety profile combines reactions from each drug alone. While more prospective studies are needed to characterize the safety of ipilimumab and nivolumab, the present work constitutes perhaps the first effort to examine the safety of these drugs and their combination based on computational evidence from real world post marketing data.
Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors. [2021]The advent of Immune Checkpoint Inhibitors (ICIs) as a standard of care for several cancers, including melanoma and head/neck squamous cell carcinoma has changed the therapeutic approach to these conditions, drawing at the same time the attention on some safety issues related to their use. To assess the incidence of psoriasis as a specific immune-related cutaneous adverse event attributing to ICIs using the Eudravigilance reporting system. All reports of adverse drug reactions (ADRs) concerning either exacerbation of psoriasis or de novo onset of psoriasis/psoriasiform reactions associated to the use of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors ipilimumab and tremelimumab, and the Programmed cell Death protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibitors nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab were identified and extracted from the Eudravigilance reporting system, during the period between the date of market licensing (for each study drug) and 30 October 2020. 8213 reports of cutaneous ADRs associated with at least one of study drug have been recorded, of which 315 (3.8%) reporting psoriasis and/or psoriasiform reactions as ADR. In 70.8% of reports patients had pre-existing disease. ICIs-related skin toxicity is a well-established phenomenon, presenting with several conditions, sustained by an immune background based on the activity of some cells (CD4+/CD8+ T-cells, neutrophils, eosinophils, and plasmocytes), inflammatory mediators, chemokines, and tumor-specific antibodies. In this setting, psoriasis represents probably the most paradigmatic model of these reactions, thus requiring adequate recognition as no guidelines on management are now available.
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. [2022]This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma.
Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study. [2021]Anti-PD-1 therapy (hereafter referred to as anti-PD-1) induces long-term disease control in approximately 30% of patients with metastatic melanoma; however, two-thirds of patients are resistant and will require further treatment. We aimed to determine the efficacy and safety of ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab) compared with ipilimumab monotherapy in patients who are resistant to anti-PD-(L)1 therapy (hereafter referred to as anti-PD-[L]1).
Immunotherapy First for BRAF-Mutant Melanoma. [2022]More people with newly diagnosed BRAFV600-mutant metastatic melanoma survive at least 2 years when they begin treatment with a combination of immunotherapies-the PD-1 inhibitor nivolumab and the CTLA4 inhibitor ipilimumab-instead of a combination of targeted therapies-the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. Researchers say the findings point to a new standard for first-line treatment.