Duvelisib + Nivolumab for Skin Cancer
Recruiting in Palo Alto (17 mi)
+17 other locations
Overseen byNeha Mehta-Shah
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial tests duvelisib and nivolumab in patients with advanced mycosis fungoides and Sezary syndrome. Duvelisib blocks cancer cell growth, and nivolumab boosts the immune system to fight cancer. The goal is to find the best dose and see if this combination works better than current treatments.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you must stop all current medications, but there are some restrictions. You cannot be on strong inhibitors or inducers of CYP3A4, and you must stop any systemic therapy for MF/SS with specific washout periods: 8 weeks for low-dose total skin electron beam therapy, 4 weeks for systemic cytotoxic agents or tumor-targeting monoclonal antibodies (except alemtuzumab, which is 16 weeks), 2 weeks or 5 half-lives for systemic retinoids and other specified agents, 2 weeks for local radiation, and 1 week for topical retinoids and other specified topical treatments. You can continue using inhaled steroids and certain topical steroids if stable for at least 4 weeks. Please consult with the trial team for guidance on your specific medications.
What data supports the idea that Duvelisib + Nivolumab for Skin Cancer is an effective treatment?
The available research shows that Nivolumab, one of the drugs in the Duvelisib + Nivolumab combination, has been effective in treating advanced melanoma, a type of skin cancer. It was the first drug of its kind to show long-term survival benefits in clinical trials for advanced melanoma patients. However, there is no specific data provided on the combination of Duvelisib and Nivolumab for skin cancer in the information available.12345
What safety data is available for the combination of Duvelisib and Nivolumab in treating skin cancer?
The provided research does not directly address the safety data for the combination of Duvelisib and Nivolumab specifically for skin cancer. However, it includes information on the safety profile of Nivolumab, which is used in combination therapies. Nivolumab has been associated with adverse reactions such as fatigue, diarrhea, constipation, nausea, musculoskeletal pain, rash, and pruritus. Additionally, dermatological adverse events have been reported with Nivolumab in combination with other drugs, such as rash and pruritus. No specific safety data for Duvelisib or its combination with Nivolumab is mentioned in the provided research.678910
Is the drug Duvelisib, Nivolumab a promising treatment for skin cancer?
Eligibility Criteria
Adults over 18 with stage IIB-IVB mycosis fungoides or Sezary syndrome who've had prior systemic therapy can join this trial. They must have certain levels of blood cells, kidney and liver function, and controlled brain metastases if present. Heart disease patients need a specific risk assessment. Participants must use effective contraception and not be pregnant or breastfeeding.Inclusion Criteria
I can take care of myself but might not be able to do heavy physical work.
I am 18 years old or older.
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or =< 5 x institutional ULN if with history of Gilbert's syndrome
See 12 more
Exclusion Criteria
I do not have an active or history of severe autoimmune disease.
I have been treated with a PI3K inhibitor before.
I have previously been treated with drugs that boost the immune system.
Treatment Details
Interventions
- Duvelisib (PI3K Inhibitor)
- Nivolumab (Checkpoint Inhibitor)
Trial OverviewThe trial is testing the combination of duvelisib (which blocks enzymes for cell growth) with nivolumab (an immunotherapy that helps the immune system attack cancer). It aims to find the best dose, benefits, and side effects compared to usual treatments for these skin cancers.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (duvelisib, nivolumab)Experimental Treatment6 Interventions
Patients receive duvelisib PO QD or BID on days 1-28 or days 1-14 and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT or CT scan at baseline. Patients also undergo punch biopsy and collection of blood samples throughout the trial.
Duvelisib is already approved in United States for the following indications:
🇺🇸 Approved in United States as Copiktra for:
- Relapsed or refractory chronic lymphocytic leukemia (CLL)
- Relapsed or refractory small lymphocytic lymphoma (SLL)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Siteman Cancer Center-South CountySaint Louis, MO
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, FL
Siteman Cancer Center at Christian HospitalSaint Louis, MO
UCHealth University of Colorado HospitalAurora, CO
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. [2021]The case was analyzed for response to nivolumab (Opdivo) monotherapy in a patient with recurrent skin melanoma (10x6x6 cm) and disease dissemination (with multiple lung metastasis), positive for BRAF mutation that followed upon the local therapy (surgical excision) and 6 cycles of adjuvant chemotherapy (at CVD regimen - cisplatin, vinblastine, dacarbazine). Histological results: melanoma. Immunohystochemical: S 100-positive; Melan A - positive; HMB45 - positive, AE1/AE3 - negative, p53 - positive in most cells, vim - positive, ɑ sma - weak in most cells, Ki67 - positive in 20%, BRAFmut, ECOG performance status 1, LDH - 1320 U/L (N
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.
Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. [2023]The addition of consolidative durvalumab to chemoradiation has improved disease control and survival in locally advanced non-small cell lung cancer (NSCLC). However, there remains a need to identify biomarkers for response to this therapy to allow for risk adaptation and personalization.
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.
Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. [2021]Current strategies to improve clinical outcomes in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog-mutant non-small-cell lung cancer (NSCLC) patients include mitogen-activated protein kinase kinase 1 inhibitor and programmed death (PD) 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint blockade combinations. Experience from treatment of melanoma suggests that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-PD-1/PD-L1 combinations improve outcomes, but similar benefits remain to be seen for treatment of NSCLC. This report describes a single center, investigator-initiated phase I/II clinical trial to compare 2 combination schedules of intermittent or continuous selumetinib (AZD6244, ARRY-142886), tremelimumab (anti-CTLA-4), and durvalumab (anti-PD-L1) treatment with historical controls in patients with previously treated, unresectable NSCLC. Forty patients will be accrued at the University of Texas M.D. Anderson Cancer Center. Primary objectives include maximum tolerated dose (dose escalation phase) and progression-free survival (dose expansion phase). Secondary objectives include response rate according to Response Evaluation Criteria In Solid Tumors version 1.1, disease control rate, overall survival, safety, and duration of response. Exploratory objectives are to assess biomarkers of response and resistance on the basis of biopsies and peripheral blood taken before and after treatment using immune profiling, transcriptome, and protein readouts.
Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. [2022]Aim: This paper presents the reported dermatological adverse events (AEs) associated with approved combinations of immunotherapy with drugs of the same class, or in combination with targeted therapy or chemotherapy. Materials & methods: PubMed was used as an electronic database, and a total of 29 articles were reviewed which reported dermatological AEs following combination therapies with nivolumab, ipilimumab, axitinib, pembrolizumab, lenvatinib, avelumab, atezolizumab, carboplatin, etoposide, paclitaxel, bevacizumab, pemetrexed, cisplatin and durvalumab. Results: The dermatological AEs reported were mutually inclusive and the highest incidence of specific AEs was seen in the following combinations: rash in the nivolumab/ipilimumab and lenvatinib/pembrolizumab combinations, pruritus in the atezolizumab/nab-paclitaxel combination, dry skin and palmar-plantar erythrodysesthesia in the axitinib/pembrolizumab combination, and alopecia and severe skin reactions in the pembrolizumab/carboplatin/paclitaxel combination. Conclusion: Knowledge of such side effects is of benefit when choosing an optimal treatment regimen and should be integrated into the monitoring and follow-up phases of treatment.
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.
[Treatment-related Skin Toxicity Caused by Programmed Death-1 Inhibitor Nivolumab: A Case Report]. [2020]Nivolumab is an checkpoint inhibitor combining with programmed death-1 (PD-1) receptor on T cells, which can block the interactions between PD-1 and programmed death ligands (PD-L), including PD-L1 and PD-L2. And then block the immunosuppression mediated by the PD-1 pathway. The aim of the study is to investigate the clinical manifestations, diagnosis, treatment and prognosis of treatment-related skin toxicity caused by PD-1 inhibitor Nivolumab.
First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p
Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.
Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. [2022]Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy. Based on these results, the combination of nivolumab and ipilimumab has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. So far, there have been no data concerning the combination of nivolumab and ipilimumab in squamous cell head and neck cancer. We here present the case of a 46-year-old male with refractory squamous cell head and neck cancer, who was successfully treated with the PD-1 inhibitor nivolumab in combination with the anti-CTLA4 antibody ipilimumab.
Nivolumab-induced hypothyoidism with consequent hypothyroid related myopathy. [2020]Nivolumab is a fully human IgG4 programmed death 1 immune checkpoint inhibitor (ICI) antibody that has anti-tumor activity by selectively blocking the interaction of the programmed death 1 receptor with its two known programmed death ligands PD-L1 and PD-L2. In doing so, this immune checkpoint inhibitor removes the negative signal stifling T cell activation and proliferation within the tumor microenvironment and demonstrates favorable antitumor activity.