RECRUITING

Metronomic Cyclophosphamide With Pembrolizumab in Checkpoint Inhibitor Refractory Melanoma

Conditions

Melanoma Melanoma Stage III Melanoma (Skin)Melanoma Stage IV Melanoma, Stage III Skin Melanoma, Stage IV Pembrolizumab Cyclophosphamide

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase 2, single-arm, open label clinical trial determining efficacy of Cyclophosphamide and Pembrolizumab in subjects with melanoma.

Official Title

Metronomic Cyclophosphamide With Pembrolizumab in Checkpoint Inhibitor Refractory Melanoma

Quick Facts

Study Start:2024-12-23

Study Completion:2028-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06771544

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥18 years at the time of signing informed consent form (ICF) * Patients must have unresectable Stage III or Stage IV non-ocular melanoma per American Joint Committee on Cancer 8th Edition Staging Criteria not amenable to local therapy * Participants must have measurable disease by RECIST v1.1 criteria as assessed by investigator/ radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. * Participants must have Eastern Cooperative Group (ECOG) performance status score of 0, 1 or 2 at screening visit. * Life expectancy of at least 12 weeks * Adequate bone marrow, liver, and renal function * Hemoglobin ≥8.0 g/dL * Platelets ≥75/mm3 * ANC ≥1.5/mm3 * Creatinine Clearance ≥ 30mL/min Cockcroft-Gault CrCl, mL/min = (140 - age) × (weight, kg) × (0.85 if female) / (72 × Cr, mg/dL). * AST and ALT less than 3 times the Upper Limit of Normal or less than 5 times the Upper Limit of normal with liver metastases. T Bilirubin \< 3.1 mg/dL. * Recovered from toxicities of pembrolizumab, excluding endocrine toxicities * Receipt of PD-1/PD-L1 * For melanoma patients: within 6 weeks (every 3 week dosing) or 9 weeks (every 6 week dosing) prior to the first dose of the investigational therapy * Women of childbearing potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment * Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study. * Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the trial screening date until 3 months after the final dose of study intervention; cessation of birth control after this point shall be discussed with a responsible physician. * Pregnant or lactating women are prohibited from enrolling in this study. * Male participants are not allowed to donate sperm from the time of enrollment until 6 months after administration of study interventions.	* Participants with a diagnosis of ocular or metastatic uveal melanoma * Participants with a history of a malignant disease other than those being treated in this study. The following exceptions are permitted: * Malignancies that were treated curatively and have not recurred within 2 years. Shorter intervals can be considered after discussion with the Principal Investigator. * Completely resected basal cell and squamous cell skin cancers. * Any malignancy considered to be indolent and that has never required therapy, such as chronic lymphocytic leukemia. * Completely resected carcinoma in situ of any type * Participants ineligible to be retreated with pembrolizumab due to a treatment-related AE while on a prior anti-PD(L)-1 regimen that led to discontinuation of that prior therapy and would thus prevent retreatment or with an immune-related adverse event (irAE) of grade 3 or greater * Participants with known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. NOTE: Participants with previously treated brain metastases may participate provided ALL of the following apply: * Treated CNS lesions are radiographically stable (without evidence of progression for ≥ 28 days prior to the first dose of study intervention) after intervention (eg, surgery and/or radiation). * Neurologically stable and on stable dose of ≤ 10mg of prednisone equivalent steroids for at least 7 days prior to the first dose of study intervention. * Investigational or standard immunotherapy (with exception of pembrolizumab, nivolumab, or relatlimab), chemotherapy or radiation within 6-9 weeks of the first dose of the investigational therapy (see Inclusion Criteria) * Presence of B-RAF driver mutation without prior receipt of BRAF +/- MEK inhibitors, unless patient declines BRAF +/-MEK inhibition for any reason or is unable to tolerate BRAF and/or MEK inhibitors. * Participants with a known history of chronic viral infections as indicated below. If patients do not have a known history, testing is not required during the screening period to confirm the patient has an active infection. * Known HBV infection defined as hepatitis B surface antigen reactive. NOTE: Participants with HBV infection on stable anti-viral therapy for \> 4 weeks prior to the planned first study intervention and viral load confirmed as undetectable during Screening may be eligible. * Known active HCV infection defined as detectable HCV RNA (qualitative) infection. NOTE: History of HCV is not exclusionary if participant has received curative treatment and viral load is confirmed as undetectable during Screening. * Active HIV infection. Those with HIV infections on combination antiretroviral medications with stable CD4 count \>200/microliters as measured within screening time period. If the patient does not have a known history of HIV, then testing is not required during screening to confirm presence or absence of HIV. * Positive serum pregnancy test * Participants with out-of-range screening laboratory values as defined below. NOTE: Hematology evaluations must be performed \>7 days from any blood transfusion. Or blood product transfusion or from any dose of hematologic growth factor. * Glomerular filtration rate (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula) \< 30 mL/min * Total bilirubin \> 1.5 × ULN; participants with Gilbert's syndrome are excluded if total bilirubin \> 3.0 × ULN; or direct bilirubin \> 1.5 × ULN * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): \> 2.5 × ULN (\> 5 × ULN for participants with liver metastases) * Albumin \< 3.0 g/dL * Absolute neutrophil count \< 1.5 × 10\^9/L * Absolute lymphocyte count \< 0.5 × 10\^9/L * Platelet count \< 100 × 10\^9/L * Hemoglobin \< 9 g/dL * Participants with a history of allogeneic tissue/solid organ transplant

Inclusion Criteria

Exclusion Criteria

* Age ≥18 years at the time of signing informed consent form (ICF)
* Patients must have unresectable Stage III or Stage IV non-ocular melanoma per American Joint Committee on Cancer 8th Edition Staging Criteria not amenable to local therapy
* Participants must have measurable disease by RECIST v1.1 criteria as assessed by investigator/ radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
* Participants must have Eastern Cooperative Group (ECOG) performance status score of 0, 1 or 2 at screening visit.
* Life expectancy of at least 12 weeks
* Adequate bone marrow, liver, and renal function
* Hemoglobin ≥8.0 g/dL
* Platelets ≥75/mm3
* ANC ≥1.5/mm3
* Creatinine Clearance ≥ 30mL/min Cockcroft-Gault CrCl, mL/min = (140 - age) × (weight, kg) × (0.85 if female) / (72 × Cr, mg/dL).
* AST and ALT less than 3 times the Upper Limit of Normal or less than 5 times the Upper Limit of normal with liver metastases. T Bilirubin \< 3.1 mg/dL.
* Recovered from toxicities of pembrolizumab, excluding endocrine toxicities
* Receipt of PD-1/PD-L1
* For melanoma patients: within 6 weeks (every 3 week dosing) or 9 weeks (every 6 week dosing) prior to the first dose of the investigational therapy
* Women of childbearing potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment
* Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study.
* Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the trial screening date until 3 months after the final dose of study intervention; cessation of birth control after this point shall be discussed with a responsible physician.
* Pregnant or lactating women are prohibited from enrolling in this study.
* Male participants are not allowed to donate sperm from the time of enrollment until 6 months after administration of study interventions.

* Participants with a diagnosis of ocular or metastatic uveal melanoma
* Participants with a history of a malignant disease other than those being treated in this study. The following exceptions are permitted:
* Malignancies that were treated curatively and have not recurred within 2 years. Shorter intervals can be considered after discussion with the Principal Investigator.
* Completely resected basal cell and squamous cell skin cancers.
* Any malignancy considered to be indolent and that has never required therapy, such as chronic lymphocytic leukemia.
* Completely resected carcinoma in situ of any type
* Participants ineligible to be retreated with pembrolizumab due to a treatment-related AE while on a prior anti-PD(L)-1 regimen that led to discontinuation of that prior therapy and would thus prevent retreatment or with an immune-related adverse event (irAE) of grade 3 or greater
* Participants with known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. NOTE: Participants with previously treated brain metastases may participate provided ALL of the following apply:
* Treated CNS lesions are radiographically stable (without evidence of progression for ≥ 28 days prior to the first dose of study intervention) after intervention (eg, surgery and/or radiation).
* Neurologically stable and on stable dose of ≤ 10mg of prednisone equivalent steroids for at least 7 days prior to the first dose of study intervention.
* Investigational or standard immunotherapy (with exception of pembrolizumab, nivolumab, or relatlimab), chemotherapy or radiation within 6-9 weeks of the first dose of the investigational therapy (see Inclusion Criteria)
* Presence of B-RAF driver mutation without prior receipt of BRAF +/- MEK inhibitors, unless patient declines BRAF +/-MEK inhibition for any reason or is unable to tolerate BRAF and/or MEK inhibitors.
* Participants with a known history of chronic viral infections as indicated below. If patients do not have a known history, testing is not required during the screening period to confirm the patient has an active infection.
* Known HBV infection defined as hepatitis B surface antigen reactive. NOTE: Participants with HBV infection on stable anti-viral therapy for \> 4 weeks prior to the planned first study intervention and viral load confirmed as undetectable during Screening may be eligible.
* Known active HCV infection defined as detectable HCV RNA (qualitative) infection. NOTE: History of HCV is not exclusionary if participant has received curative treatment and viral load is confirmed as undetectable during Screening.
* Active HIV infection. Those with HIV infections on combination antiretroviral medications with stable CD4 count \>200/microliters as measured within screening time period. If the patient does not have a known history of HIV, then testing is not required during screening to confirm presence or absence of HIV.
* Positive serum pregnancy test
* Participants with out-of-range screening laboratory values as defined below. NOTE: Hematology evaluations must be performed \>7 days from any blood transfusion. Or blood product transfusion or from any dose of hematologic growth factor.
* Glomerular filtration rate (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula) \< 30 mL/min
* Total bilirubin \> 1.5 × ULN; participants with Gilbert's syndrome are excluded if total bilirubin \> 3.0 × ULN; or direct bilirubin \> 1.5 × ULN
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): \> 2.5 × ULN (\> 5 × ULN for participants with liver metastases)
* Albumin \< 3.0 g/dL
* Absolute neutrophil count \< 1.5 × 10\^9/L
* Absolute lymphocyte count \< 0.5 × 10\^9/L
* Platelet count \< 100 × 10\^9/L
* Hemoglobin \< 9 g/dL
* Participants with a history of allogeneic tissue/solid organ transplant

Contacts and Locations

Study Contact

Chao Family Comprehensive Cancer Center University of California, Irvine

CONTACT

1-877-827-8839

ucstudy@uci.edu

University of California Irvine Medical

CONTACT

Principal Investigator

Warren Chow, MD

PRINCIPAL_INVESTIGATOR

Chao Family Comprehensive Cancer Center

Study Locations (Sites)

Chao Family Comprehensive Cancer Center University of California, Irvine

Orange, California, 92868

United States

Collaborators and Investigators

Sponsor: University of California, Irvine

Warren Chow, MD, PRINCIPAL_INVESTIGATOR, Chao Family Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-23

Study Completion Date2028-12

Study Record Updates

Study Start Date2024-12-23

Study Completion Date2028-12

Terms related to this study

Keywords Provided by Researchers

Melanoma
Melanoma, Stage III
Skin
Melanoma, Stage IV
Pembrolizumab
Cyclophosphamide

Additional Relevant MeSH Terms

Melanoma
Melanoma Stage III
Melanoma (Skin)
Melanoma Stage IV