Cyclophosphamide + Pembrolizumab for Melanoma
Recruiting in Palo Alto (17 mi)
Overseen byWarren Chow, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of California, Irvine
Must be taking: PD-1/PD-L1
Must not be taking: Antivirals, Antiretrovirals
Disqualifiers: Ocular melanoma, CNS metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a phase 2, single-arm, open label clinical trial determining efficacy of Cyclophosphamide and Pembrolizumab in subjects with melanoma.
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, it mentions that certain treatments like investigational or standard immunotherapy, chemotherapy, or radiation should not be taken within 6-9 weeks of the first dose of the trial therapy. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drugs Cyclophosphamide and Pembrolizumab for treating melanoma?
Research shows that pembrolizumab, one of the drugs in the treatment, improves survival in patients with advanced melanoma and is superior to another drug, ipilimumab, in treating this condition. Additionally, pembrolizumab has shown promising results when used in combination with other treatments for melanoma.
12345Is the combination of Cyclophosphamide and Pembrolizumab safe for treating melanoma?
Pembrolizumab is generally well tolerated and has a favorable safety profile in treating advanced melanoma, with common side effects including fatigue, rash, itching, and diarrhea. Less common but more serious side effects can include immune-related issues like hypothyroidism, colitis, hepatitis, and pneumonitis. Cyclophosphamide is not specifically mentioned in the provided research, so its safety in combination with pembrolizumab is not detailed here.
678910How is the drug combination of Cyclophosphamide and Pembrolizumab unique for treating melanoma?
This treatment combines Cyclophosphamide, a chemotherapy drug, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. Pembrolizumab has shown improved survival outcomes in advanced melanoma, and combining it with Cyclophosphamide may enhance its effectiveness by potentially boosting the immune response.
13111213Eligibility Criteria
Adults with advanced non-ocular melanoma who've previously had PD-1/PD-L1 therapy can join. They need measurable disease, an ECOG score of 0-2, and a life expectancy over 12 weeks. Participants must have good organ function and agree to contraception. Exclusions include ocular melanoma, severe prior pembrolizumab side effects, untreated brain metastases, certain viral infections, or recent other cancer treatments.Inclusion Criteria
I agree to use effective birth control during and 3 months after the study.
My cancer can be measured by scans and has grown in previously treated areas.
I can take care of myself and am up and about more than half of my waking hours.
+15 more
Exclusion Criteria
I have been diagnosed with a type of eye cancer called uveal melanoma.
I stopped a previous cancer treatment due to severe side effects.
My cancer has a B-RAF mutation and I haven't taken, or can't take, BRAF/MEK inhibitors.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Pembrolizumab 200mg IV every 21 days or 400 mg IV every 42 days and Cyclophosphamide 50mg PO daily on days 1-14 every 21 days
Up to 3 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
This phase 2 trial tests Cyclophosphamide combined with Pembrolizumab in patients whose melanoma didn't respond to checkpoint inhibitors. It's open-label so everyone knows what treatment they're getting and aims to see how effective this combination is.
1Treatment groups
Experimental Treatment
Group I: Pembrolizumab + CyclophosphamideExperimental Treatment2 Interventions
Pembrolizumab 200mg IV every 21 days or 400 mg IV every 42 days Cyclophosphamide 50mg PO daily on days 1-14 every 21 days for melanoma patients
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Chao Family Comprehensive Cancer Center University of California, IrvineOrange, CA
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Who Is Running the Clinical Trial?
University of California, IrvineLead Sponsor
References
A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. [2021]Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted.
Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. [2020]Immunotherapy combination treatments can improve patient outcomes. Epacadostat, an IDO1 selective inhibitor, and pembrolizumab, a PD-1 inhibitor, showed promising antitumour activity in the phase 1-2 ECHO-202/KEYNOTE-037 study in advanced melanoma. In this trial, we aimed to compare progression-free survival and overall survival in patients with unresectable stage III or IV melanoma receiving epacadostat plus pembrolizumab versus placebo plus pembrolizumab.
Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. [2018]The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program.
Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. [2021]The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy.
Pembrolizumab superior to ipilimumab in melanoma. [2017]In the first randomized trial to compare FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembrolizumab yielded significantly better treatment outcomes than ipilimumab.
Pembrolizumab in the management of metastatic melanoma. [2020]Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that plays a major role in the treatment of advanced melanoma. Through blockade of PD-1, it leads to an increase in effector T-cell activity in the tumor microenvironment. Clinical trial outcomes for pembrolizumab in addition to pharmacokinetics, pharmacodynamics and safety of the compound are discussed in this article. Phase I trials have demonstrated safety and efficacy of pembrolizumab in advanced, pretreated melanoma patients. When compared with chemotherapy in a Phase II trial of ipilimumab-refractory patients, those treated with pembrolizumab showed superior progression-free survival. In addition, in the pivotal Phase III trial pembrolizumab improved overall survival compared with ipilimumab in patients naive to immune checkpoint inhibition. Pembrolizumab is well tolerated and has a favorable safety profile. Common adverse events are fatigue, rash, itching and diarrhea. Less frequent immune-related adverse events include hypothyroidism, colitis, hepatitis and pneumonitis.
Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]We aimed to characterize the safety profile of pembrolizumab in advanced melanoma patients at our center to better reflect 'real-world' data on anti-PD-1 inhibitors.
Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy. [2023]Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life-threatening immune-related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies.
Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab. [2017]Currently, limited data exist on the safety of pembrolizumab in patients with metastatic melanoma who have developed severe immune-related adverse events following treatment with ipilimumab. We report a 45-year-old male patient with BRAF-mutant metastatic melanoma who discontinued treatment with ipilimumab due to treatment-related grade 3 colitis and was subsequently treated with the anti-programmed cell death 1 protein (PD-1) antibody pembrolizumab. He has been on treatment with pembrolizumab for more than 20 months with no major toxicities and has achieved an objective partial response, which is ongoing.
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]On December 18, 2015, the FDA granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma based on results of two randomized, open-label, active-controlled clinical trials. In trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 or 3 weeks until disease progression or ipilimumab 3 mg/kg every 3 weeks for up to four doses. In trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg i.v. every 3 weeks or to investigator's choice of chemotherapy. In trial PN006, patients randomized to pembrolizumab demonstrated a statistically significant improvement in overall survival compared with ipilimumab [every-2-week arm: hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.47-0.83; P < 0.001; every-3-week arm: HR = 0.69; 95% CI, 0.52-0.90; P = 0.004]. In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (≥2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of tumor response-based endpoints using RECIST or immune-related RECIST. Clin Cancer Res; 23(19); 5661-5. ©2017 AACR.
Cost-utility analysis of Pembrolizumab compared to other alternative immunotherapy and chemotherapy treatments for patients with advanced melanoma in Iran. [2023]Immunotherapy drugs like Pembrolizumab have shown significant improvements in treatment outcomes of advanced melanoma. This study aimed to evaluate the cost-utility of Pembrolizumab compared to other immunotherapy and chemotherapy drugs in the first-line treatment of advanced melanoma in Iran.
Challenging the standard of care in advanced melanoma: focus on pembrolizumab. [2020]The last several years have seen a dramatic rise in the number of effective therapies that have been shown to improve survival outcomes for patients with advanced melanoma. Among these treatments are the immune checkpoint inhibitors, a new class of immunotherapy, that have demonstrated the ability to improve both response rates and survival outcomes. Pembrolizumab, an immune checkpoint inhibitor that blocks the negative regulatory PD-1 receptor on T-cell lymphocytes, has shown improved efficacy compared to standard therapies with an acceptable tolerability profile. Additionally, this agent is being evaluated in adjuvant and combination trial strategies that have great potential to further advance outcomes. This review focuses on the advances that pembrolizumab has made in melanoma and what studies are upcoming that could change the future of melanoma treatment yet again.
Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]To investigate the clinical application value of Pembrolizumab (PEM) in the treatment of advanced cutaneous malignant melanoma (ACMM).