Overview

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.

Eligibility

Inclusion Criteria for Dose escalation zeaxanthin monotherapy

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).
          6. Ability to understand and the willingness to sign a written informed consent.
          7. Measurable disease is not required but evaluable disease is required.
          8. Life expectancy of at least 3 months
        Exclusion Criteria for Dose escalation zeoxanthin monotherapy
          1. 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 may not be receiving any other investigational agents or concomitant
             chemotherapy or radiation therapy. Hormonal therapy is not exclusionary.)
          2. Patients with active brain metastases requiring palliation with steroids and not
             stable for at least 4 weeks post radiation therapy or surgery.
          3. Leptomeningeal carcinomatosis
          4. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to zeaxanthin.
          5. 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.
          6. 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.
          7. 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
          8. Inability to swallow pills.
        Inclusion Criteria for dose escalation zeoxanthin 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).
          7. Ability to understand and the willingness to sign a written informed consent.
          8. Measurable disease is not required but evaluable disease is required
          9. Life expectancy of at least 3 months
        Exclusion Criteria for zeoxanthin plus pembrolizumab
          1. Patients who have had immunotherapy, chemotherapy or radiotherapy within 21 days prior
             to entering the study or those who have not recovered to grade1 or lower 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.
          2. Prior grade 3 or greater immune mediated toxicity related to PD-1 or PD-L1 inhibitor.
             Prior grade 2 or higher colitis, diarrhea, hepatitis, neurologic, cardiac, immune
             mediated toxicity related to PD-1 or PD-L1 inhibitor. Exceptions include vitiligo and
             controlled endocrinopathies.
          3. Patients may not be receiving any other investigational agents or concomitant
             chemotherapy or radiation therapy.
          4. Patients taking oral steroids at or greater than the equivalent of 10 milligrams of
             oral prednisone daily.
          5. Inability to swallow pills.
          6. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to zeaxanthin.
          7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris,
             uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.
          8. 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
          9. Patients with active brain metastases requiring palliation with steroids not stable
             for at least 4 weeks post radiation therapy or surgery
         10. Leptomeningeal carcinomatosis
         11. Patients with another primary malignancy not in remission for at least 3 years.
             Exceptions include non-melanoma skin cancer, curatively treated localized prostate
             cancer with normal prostate specific antigen, low risk prostate cancer followed
             expectantly, resected stage 1 colon cancer, resected stage 1 breast cancer, cervical
             carcinoma in situ on biopsy, melanoma in situ resected, or squamous intraepithelial
             lesion on PAP smear.