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Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Zeaxanthin administered orally on daily basis.

Zeaxanthin administered orally on daily basis in addition to intravenous pembrolizumab infused every 42 days at fixed dose of 400 mg.

The doses of zeaxanthin will be based on weight starting with 2 milligrams of zeaxanthin per kilogram of your 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.

Zeaxanthin

The doses of zeaxanthin will be based on weight starting with 2 milligrams of zeaxanthin per kilogram of your 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.

The dose of pembrolizumab will be administered at a fixed dose of 400 milligrams intravenous every 6 weeks which is an FDA approved dosing schedule to treat cancer patients with pembrolizumab.

Zeaxanthin Plus Pembrolizumab

Kathleen Sayles

Robyn Puso

Philip Friedlander, MD

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.

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.

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

A Phase I Study to Determine the Safety and Recommended Phase 2 Dosing of Zeaxanthin Alone or in Combination With Pembrolizumab in Patients With Metastatic Solid Tumors

Measured by changes in immune cell populations and CD31 vascularization between baseline and on treatment tumor biopsy specimens

Measured by changes in the percentage of different immune cell populations between baseline and on treatment blood specimens

Measured by changes in percentage of different immune cell populations between baseline and on treatment blood specimens

Measured by changes in PBMC samples obtained at baseline and on treatment with PBMCs subjected to bulk RNA sequencing

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

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

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

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

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

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

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

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

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

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

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

Pharmacokinetics of zeaxanthin as measured by AUC

Spots Global Cancer Trial Database for zeaxanthin plus pembrolizumab