Metronomic Cyclophosphamide With Pembrolizumab in Checkpoint Inhibitor Refractory Melanoma

ConditionsMelanoma Melanoma Stage III Melanoma (Skin)Melanoma Stage IV

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity of California, Irvine

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

Participants with a diagnosis of ocular or metastatic uveal melanoma

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.

Trial design

Design model

Single group

Treatments tested in this trial

Pembrolizumab
Drug
Given IV
Cyclophosphamide
Drug
Given PO

Treatment groups

14 Participants

are divided into 1 treatment group

Group A: Pembrolizumab + CyclophosphamideExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame

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.

Time frame

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.

Time frame

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..

Time frame

Up to 3 years

Secondary outcomes

Objective Response Rate (ORR) by iRECIST

Sum of Complete Response (CR) and Partial Response (PR) by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST). Per iRECIST: Immune Complete Response (iCR) is defined the complete disappearance of the tumor and non-tumor lesions; Immune Partial Response (iPR) is defined as a 30% tumor load decrease from baseline; Immune Stable Disease (iSD) is defined as when neither iCR nor iPR apply and there is no tumor progression; Unconfirmed Progressive Disease (iUPD) is defined as a 20% or greater increase in tumor burden or an appearance of a new target or non-target lesion; Confirmed Progressive Disease (iCPD) is defined as an increase of 5mm or greater in target tumor burden, or new target lesion, or any increase in non-target disease; Immune Best overall Response (IBOR) is defined as the best timepoint response recorded from the start to the end of the immunotherapy. ORR based on iRECIST refers to the percentage of patients in a clinical trial who experience a measurable

Time frame

Up to 3 years

Clinical Benefit Rate

Complete Response, Partial Response, and \>6 months of stable disease as evaluated by RECIST v 1.1 and immune RECIST (iRECIST). 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. Stable Disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study

Time frame

Up to 3 years

Overall Survival

Survival rate of subjects who received at least one dose of Pembrolizumab with Cyclophosphamide

Time frame

Up to 3 years

Progression Free Survival

Survival rate of subjects who received at least one dose of Pembrolizumab with Cyclophosphamide without Progression of their disease.

Time frame

Up to 3 years.

Other outcomes

Comparison of Phenotype and T-Cell Function

Compare the Phenotype of and T-cell Function of Paired Biopsies before and after Investigational Treatment

Time frame

Up to 3 years

Comparative Quantitative analysis of T-Cell Repertoire

Comparative Quantitative analysis of T-Cell Repertoire in Paired Biopsies before and after Investigational Treatment

Time frame

Up to 3 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, Irvine

Lead sponsor

Source ClinicalTrials.gov

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