Zeaxanthin

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

Objective

For dose escalation part A, the primary objective is to evaluate the safety and tolerability of escalating doses of zeaxanthin for patients with metastatic solid tumor, and to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) and dose-limiting toxicity (DLT). For dose escalation part B, the primary objective is to evaluate the safety and tolerability of escalating doses of zeaxanthin in patients being treated with pembrolizumab who have metastatic solid tumor for which pembrolizumab is FDA-approved and to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) and dose-limiting toxicity (DLT).

Study Arms

  • Experimental: Zeaxanthin Monotherapy

  • Experimental: Zeaxanthin plus Pembrolizumab

Eligibility

  1. 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).
  2. Age ≥ 18 years.
  3. Performance status ECOG 0, 1 or 2
  4. 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
  5. 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:

  1. 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.
  2. 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:

  1. Has not undergone a hysterectomy or bilateral oophorectomy
  2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

  3. Ability to understand and the willingness to sign a written informed consent.

  4. Measurable disease is not required but evaluable disease is required.
  5. Life expectancy of at least 3 months

Inclusion Criteria for dose escalation zeaxanthin plus pembrolizumab

  1. 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).
  2. 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.
  3. Age ≥ 18 years.
  4. Performance status ECOG 0, 1or 2.
  5. Adequate organ and marrow function as describe below:
    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcl
    • Total bilirubin) ≤ 1.5 x normal institutional limits excluding patients with confirmed Gilbert's syndrome
    • AST (SGOT)/ALT (SPGT) ≤ 3 x institutional upper limit of normal
    • Creatinine ≤ 1.5 x the institutional upper limit of normal
  6. 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:

  1. 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.
  2. 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:

  1. Has not undergone a hysterectomy or bilateral oophorectomy
  2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  1. Ability to understand and the willingness to sign a written informed consent.
  2. Measurable disease is not required but evaluable disease is required
  3. Life expectancy of at least 3 months

NCT ID

NCT05232409

Want to learn more? Visit ClinicalTrials.gov.

Status
Open and enrolling
Start Date