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Determine Safety & Recommended Phase 2 Dosing of Zeaxanthin Alone or in Combination w/Pembrolizumab in Patients With Metastatic Cancer

Phase 1
Recruiting
Conditions
Cancer Metastatic
Metastatic Solid Tumor
Interventions
Biological: Zeaxanthin
Combination Product: Zeaxanthin Plus Pembrolizumab
Registration Number
NCT05232409
Lead Sponsor
Valley Health System
Brief Summary

The purpose of the research is to determine the highest dose of an oral compound called zeaxanthin that can be safely taken each day in patients with advanced cancer, the toxicity profile of zeaxanthin, and the dose of zeaxanthin to use in future cancer clinical trials.

Detailed Description

The primary purpose of the study is to determine the safety and optimal dosing of zeaxanthin. Effects on tumor growth will also be looked at but as a secondary endpoint. This study will use a 3+3 design which means that 3 people will receive a certain dose of zeaxanthin and if well tolerated then the next group of people will receive a higher dose. This dose escalation will continue until the highest dose allowed by the study is reached, or a dose is found that is felt not to be safe. If at a given dose one of the three people develops a severe side effect, then three more people will be treated at that dose. If no additional severe side effects develop, then the dose escalation will continue. If two people at a given dose develop severe side effects, that dose will be considered dose limiting and escalation will stop. The doses of zeaxanthin will be based on weight starting with 2 milligrams of zeaxanthin per kilogram of body weight (mg/kg) followed by 4 mg/kg, 6 mg/kg, and finally 8 mg/kg. If a dose level is found to be unsafe, then a new group of patients will be treated at the midpoint dose between the not tolerated dose and the last tolerated dose. Zeaxanthin is supplied as 50 milligram capsules and a person's dose will be rounded to the nearest 50 milligrams.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
72
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Zeaxanthin MonotherapyZeaxanthinZeaxanthin administered orally on daily basis.
Zeaxanthin plus PembrolizumabZeaxanthin Plus PembrolizumabZeaxanthin administered orally on daily basis in addition to intravenous pembrolizumab infused every 42 days at fixed dose of 400 mg.
Primary Outcome Measures
NameTimeMethod
Zeaxanthin monotherapy (continued)Toxicities experienced within 28 days of zeoxanthin initiation

Rate of Dose Limiting Toxicity (DLT) Based on CTEP Active Version (version 5.0) of the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) in patients with unresectable advanced solid tumors treated with zeaxanthin

Zeaxanthin plus PembrolizumabUp to 20 weeks for each dosing cohort

Recommended maximum tolerated dose

Highest dose of zeoxanthin that does not cause dose limiting toxicity in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumab

Zeaxanthin monotherapyUp to 20 weeks for each dosing cohort

Recommended maximum tolerated dose

Highest dose of zeaxanthin that does not cause dose limiting toxicity in patients with unresectable advanced solid tumors treated with zeaxanthin

Zeaxanthin plus Pembrolizumab (continued)Toxicities experienced within 42 days of zeaxanthin plus pembrolizumab initiation

Rate of Dose Limiting Toxicity (DLT)

Based on CTEP Active Version (version 5.0) of the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumab

Secondary Outcome Measures
NameTimeMethod
The disease control rate (DCR) in patients with unresectable advanced solid tumors treated with zeaxanthinWeek 8 and Week 24

Percentage of patients with complete response, partial response, or stable disease according to RECIST v1.1 measured at 2 months and 6 months after initiation of zeaxanthin treatment

The progression free survival (PFS) for zeaxanthin plus pembrolizumab in in patients with unresectable advanced solid tumorsUp to 24 months

The PFS rate for zeaxanthin in patients with unresectable advanced solid tumors as measured by RECIST v1.1

The maximal plasma concentration of zeaxanthin in patients treated with zeoxanthinPharmacokinetic (PK) sampling will be performed on Day 1, 2, 8, 15,22, 28, 56, 84

To evaluate the effect of multiple doses of zeaxanthin on the steady state pharmacokinetics of zeoxanthin in patients with unresectable advanced solid tumors treated with zeaxanthin

The duration of response (DR) in patients with unresectable advanced solid tumors treated with zeaxanthin36 months

The DR by RECIST v1.1 of zeaxanthin in patients with unresectable advanced solid tumors

Area under the curve (AUC) of zeaxanthin in patients with unresectable advanced solid tumors treated with zeaxanthinPharmacokinetic (PK) sampling will be performed on Day 1, 2, 8, 15,22, 28, 56, 84

Pharmacokinetics of zeaxanthin as measured by AUC

The response rate (ORR) of zeaxanthin in patients with unresectable advanced solid tumors36 months

The ORR by RECIST v1.1 of zeaxanthin in patients with unresectable advanced solid tumors Duration of response: duration from date of initial attainment of CR or PR to date of progression, censoring at death or lost to follow-up Disease Control rate: percent of patients who develop CR, PR, or stable disease as best response as determined by RECIST v1.1 measured at 2 months and 6 months after initiation of study treatment Progression Free Survival: duration of time in months from the initiation of study treatment to date of progression, censoring at death or lost to follow-up.

The response rate of zeaxanthin plus pembrolizumab in patients with unresectable advanced solid tumors36 months

The ORR by RECIST v1.1 of zeaxanthin plus pembrolizumab in patients with unresectable advanced solid tumors

The duration of response in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumab36 months

The DR by RECIST v1.1 of zeaxanthin plus pembrolizumab in patients with unresectable advanced solid tumors

The disease control rate (DCR) in patients with unresectable advanced solid tumors treated with zeaxanthin plus zeaxanthinWeek 8 and Week 24

Percentage of patients with complete response, partial response, or stable disease according to RECIST v1.1 measured at 2 months and 6 months after initiation of zeaxanthin plus pembrolizumab treatment

The progression free survival (PFS) for zeaxanthin in in patients with unresectable advanced solid tumorsUp to 24 months

The PFS rate for zeaxanthin in patients with unresectable advanced solid tumors as measured by RECIST v1.1

The maximal plasma concentration of zeoxanthin in patients treated with zeoxanthin plus pembrolizumabPharmacokinetic (PK) sampling will be performed on Day 1, 2, 8, 15,22, 43, 64

To evaluate the effect of multiple doses of zeoxanthin on the steady state pharmacokinetics of zeoxanthin in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumab

Area under the curve (AUC) of zeaxanthin in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumabPharmacokinetic (PK) sampling will be performed on Day 1, 2, 8, 15,22, 28, 56, 84

Pharmacokinetics of zeaxanthin as measured by AUC

Trial Locations

Locations (1)

The Valley Hospital-Luckow Pavilion

🇺🇸

Paramus, New Jersey, United States

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