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

NCT05232409 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20.0046
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer Metastatic; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Zeaxanthin monotherapy

  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

  Up to 20 weeks for each dosing cohort

• Zeaxanthin monotherapy (continued)

  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

  Toxicities experienced within 28 days of zeoxanthin initiation

• Zeaxanthin plus Pembrolizumab

  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

  Up to 20 weeks for each dosing cohort

• Zeaxanthin plus Pembrolizumab (continued)

  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

  Toxicities experienced within 42 days of zeaxanthin plus pembrolizumab initiation

Secondary Outcomes (12)

• The response rate (ORR) of zeaxanthin in patients with unresectable advanced solid tumors

  36 months

• The response rate of zeaxanthin plus pembrolizumab in patients with unresectable advanced solid tumors

  36 months

• The duration of response (DR) in patients with unresectable advanced solid tumors treated with zeaxanthin

  36 months

• The duration of response in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumab

  36 months

• The disease control rate (DCR) in patients with unresectable advanced solid tumors treated with zeaxanthin

  Week 8 and Week 24

Other Outcomes (6)

• On treatment biopsy for evidence of increased immune cell infiltration and vascularization to zeaxanthin in patients with unresectable advanced solid tumors treated with zeaxanthin

  Up to 36 months

• On treatment biopsy for evidence of increased immune cell infiltration and vascularization to zeoxanthin in patients with unresectable advanced solid tumors treated with zeaxanthin plus pembrolizumab

  Up to 36 months

• On treatment percentage changes in immune cell composition in peripheral blood in patients with unresectable advanced solid tumors treated with zeaxanthin

  Up to 36 months

Study Arms (2)

Zeaxanthin Monotherapy

EXPERIMENTAL

Zeaxanthin administered orally on daily basis.

Biological: Zeaxanthin

Zeaxanthin plus Pembrolizumab

EXPERIMENTAL

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

Combination Product: Zeaxanthin Plus Pembrolizumab

Interventions

Zeaxanthin BIOLOGICAL

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 Monotherapy

Zeaxanthin Plus Pembrolizumab COMBINATION_PRODUCT

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

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage IV or unresectable stage 3 histologically confirmed solid tumor malignancy refractory to all standard therapies known to provide clinical benefit (unless the therapy is contraindicated or intolerable) in the opinion of the treating investigator for his/her tumor type. Subjects are not required to have received systemic therapies that have response rates under 20% with no associated survival benefit (for example DTIC chemotherapy and high dose Interleukin-2 in melanoma patients).
• Age ≥ 18 years.
• Performance status ECOG 0, 1 or 2
• Adequate organ and marrow function as describe below:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcl
• Total bilirubin \< 1.5 x the normal institutional limits excluding patients with confirmed Gilbert's syndrome
• AST (SGOT)/ALT (SPGT) ≤ 3 x the institutional upper limit of normal (ULN)
• Creatinine ≤ 1.5 x the institutional upper limit of normal
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Recommended methods of birth control are:
• The consistent use of an approved hormonal contraception (birth control pill/patches, rings), An intrauterine device (IUD), Contraceptive injection (Depo-Provera), Double barrier methods (Diaphragm with spermicidal gel or condoms with contraceptive foam), Sexual abstinence (no sexual intercourse) or Sterilization.
• Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 90 days after completion of therapy
• A Female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets at least one of the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 21 days prior to initiating study treatment or those who have not recovered to grade 1 or less from adverse events due to agents administered more than 21 days earlier excluding alopecia, gd 2 fatigue, gd 2 hearing loss from platinum agent, and endocrinopathies on stable replacement therapy.
• Patients with active brain metastases requiring palliation with steroids and not stable for at least 4 weeks post radiation therapy or surgery.
• Leptomeningeal carcinomatosis
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to zeaxanthin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with another primary malignancy not in remission for at least 3 years. Exceptions include nonmelanoma skin cancer, curatively treated localized prostate cancer with normal prostate specific antigen, low risk prostate cancer followed expectantly, stage I colorectal cancer resected, resected stage 1 breast cancer cervical carcinoma in situ on biopsy, melanoma in situ resected, or squamous intraepithelial lesion on PAP smear.
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Women of child bearing potential must have a negative serum or urine pregnancy test prior to the first dose of study treatment
• Inability to swallow pills.
• Stage IV or unresectable stage 3 histologically confirmed solid tumor malignancy for which pembrolizumab is FDA approved and progressed on prior PD-1 or PD-L1 therapy and if indicated for cancer type refractory to all standard therapies known to provide clinical benefit (unless the therapy is contraindicated or intolerable) in the opinion of the treating investigator for his/her tumor type. Subjects are not required to have received systemic therapies that have response rates under 20% with no associated survival benefit (for example DTIC chemotherapy and high dose Interleukin-2 in melanoma patients).
• Patients must have had symptomatic or radiographic progression during or following treatment with a PD-1 or PD-L1 inhibitor. This is defined as imaging obtained subsequent to initiation of PD-1 or PD-L1 inhibitor demonstrating a new lesion that is consistent with metastasis or growth of a preexisting metastasis which the treating physician felt reflected tumor progression and therefore discontinued the immunotherapy. . Symptomatic progression refers to development of worsening bone pain related to bone metastasis that cannot be accurately measured on imaging and for which the treating physician had discontinued the immunotherapy.
• Age ≥ 18 years.
• Performance status ECOG 0, 1or 2.
• Adequate organ and marrow function as describe below:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcl

Sponsors & Collaborators

• Valley Health System: lead

Study Sites (1)

The Valley Hospital-Luckow Pavilion

Paramus, New Jersey, 07652, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Zeaxanthins; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthophylls; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Philip Friedlander, MD

  The Valley Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathleen Sayles

CONTACT

201-634-5792; ksayles@valleyhealth.com

Robyn Puso

CONTACT

201-634-5792; rpuso@valleyhealth.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: February 9, 2022
• Study Start: April 17, 2022
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2026
• Last Updated: April 20, 2023

Record last verified: 2023-04

Locations

US (1)