Recruiting
Phase 2

Metronomic Cyclophosphamide & Pembrolizumab

Sponsor:

UCLA

Code:

NCT06771544

Conditions

Melanoma

Melanoma Stage III

Melanoma (Skin)

Melanoma Stage IV

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

Cyclophosphamide

Study Details

Brief summary:

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

Conditions

Melanoma

Melanoma Stage III

Melanoma (Skin)

Melanoma Stage IV

Study ID

NCT06771544

Start date

Dec 23, 2024

Status verified date

Mar, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion 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 ≥9.0 g/dL
  • Platelets ≥100/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.
  • Has progressed on a prior PD-1/PD-L1 treatment
  • Recovered from toxicities of pembrolizumab to Grade ≤1, excluding endocrine toxicities
  • Prior Receipt of PD-1/PD-L1 therapy within 9 weeks 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.

Exclusion Criteria:

  • 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.
  • Any prior investigational or standard cancer therapy, with exception of PD-1/PD-L1 (includes nivolumab + Relatlimab) therapy, 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
  • Albumin < 3.0 g/dL
  • Absolute lymphocyte count < 0.5 × 10\^9/L
  • Participants with a history of allogeneic tissue/solid organ transplant

Study Design

Enrollment

14 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pembrolizumab + Cyclophosphamide

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

Interventions

Pembrolizumab

Given IV

Cyclophosphamide

Given PO

Primary outcome measure

  • Objective Response Rate (ORR) by RECIST v1.1 [ Time Frame: Up to 3 years ]
  • Number of Patients with Adverse Events [ Time Frame: Up to 3 years ]
  • Number of Patients with Immune Related Adverse Events [ Time Frame: Up to 3 years ]
  • Number of Patients who Discontinued Treatment Due to Reported Adverse Events [ Time Frame: Up to 3 years ]
  • Comparative Analysis of Immune Cells [ Time Frame: Up to 3 years ]

Central Contacts and Locations

Central contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

1-877-827-8839ucstudy@uci.edu

Locations

Chao Family Comprehensive Cancer Center University of California, Irvine

Recruiting

Orange, California, United States, 92868

Contacts

Warren Chow, MD

877-827-8839ucstudy@uci.edu

More Information

Sponsor

University of California, Irvine

Last update posted

Mar 10, 2026

Last verified

Mar, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, Irvine on 2026-03-10.