Metronomic Cyclophosphamide With Pembrolizumab in Checkpoint Inhibitor Refractory Melanoma

NCT06771544 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 6168UCI 22-49
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Objective Response Rate (ORR) by RECIST v1.1

  Sum of Complete Response (CR) and Partial Response (PR) by RECIST v 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR

  Up to 3 years

• Number of Patients with Adverse Events

  Number of Patients who received at least one dose of Pembrolizumab with Cyclophosphamide with any reported Adverse Events (AEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.

  Up to 3 years

• Number of Patients with Immune Related Adverse Events

  Number of Patients who received at least one dose of Pembrolizumab with Cyclophosphamide with reported immune related AEs (irAEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.

  Up to 3 years

• Number of Patients who Discontinued Treatment Due to Reported Adverse Events

  Number of Patients who received at least one dose of Pembrolizumab with Cyclophosphamide requiring discontinuation of therapy due to reported AEs using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs..

  Up to 3 years

• Comparative Analysis of Immune Cells

  Mean, median, percentage and total counts of immune T cell subsets pre-treatment and after 2 three-week cycles of metronomic cyclophosphamide and pembrolizumab.

  Up to 3 years

Secondary Outcomes (5)

• Objective Response Rate (ORR) by iRECIST

  Up to 3 years

• Clinical Benefit Rate

  Up to 3 years

• Overall Survival

  Up to 3 years

• Progression Free Survival

  Up to 3 years.

• Duration of Response

  Up to 3 years

Other Outcomes (2)

• Comparison of Phenotype and T-Cell Function

  Up to 3 years

• Comparative Quantitative analysis of T-Cell Repertoire

  Up to 3 years

Study Arms (1)

Pembrolizumab + Cyclophosphamide

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Cyclophosphamide

Interventions

Pembrolizumab DRUG

Given IV

Pembrolizumab + Cyclophosphamide

Cyclophosphamide DRUG

Given PO

Pembrolizumab + Cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

Chao Family Comprehensive Cancer Center University of California, Irvine

Orange, California, 92868, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Warren Chow, MD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

CONTACT

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

University of California Irvine Medical

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: HS Clinical Professor and Associate Director for Clinical Science

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 13, 2025
• Study Start: December 23, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

US (1)