Clinical Trials /

Pembrolizumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma

NCT03200847

Description:

This is a Phase I/Ib investigator-initiated open label of the combination of VESANOID and pembrolizumab treatment.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
  • Official Title: Pembrolizumab and All-Trans Retinoic Acid in Combination Treatment of Advanced Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 16-1080.cc
  • NCT ID: NCT03200847

Conditions

  • Stage IV Melanoma
  • Stage III Melanoma
  • Advanced Melanoma

Interventions

DrugSynonymsArms
Pembrolizumab with All-Trans Retinoic AcidVESANOID, KeytrudaPembrolizumab with All-Trans Retinoic Acid

Purpose

This is a Phase I/Ib investigator-initiated open label of the combination of VESANOID and pembrolizumab treatment.

Detailed Description

      Primary Objective

        -  To identify the MTD and RP2D of the combination of pembrolizumab and ATRA.

      Secondary Objective:

        -  Describe the safety and toxicity of combined treatment with pembrolizumab and all-trans
           retinoic acid (ATRA) [brand name VESANOID] in melanoma patients.

        -  To assess the anti-tumor activity in terms of a). The reduction in MDSC
           (immunosuppressive myeloid -derived suppressor cells) frequency and suppressive function
           (measured as a continuous variable)in peripheral blood of advanced melanoma patients
           undergoing pembrolizumab and VESANOID combination therapy. b). progression free
           survival.

      Exploratory Objective

        -  To determine the clinical outcomes with tumor-specific T cell responses.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab with All-Trans Retinoic AcidExperimentalPatients will receive pembrolizumab infusions every three weeks. Patients will also receive 3 days of all-trans retinoic acid treatment surrounding each of the first 4 infusions of pembrolizumab, beginning one day prior to the infusion (a total of 12 days of all-trans retinoic acid).
  • Pembrolizumab with All-Trans Retinoic Acid

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis of advanced melanoma (unresectable Stage III or Stage IV Melanoma).

          2. Planned standard treatment with pembrolizumab.

          3. Be willing and able to provide written informed consent for the trial.

          4. State willingness to comply with all study procedures and be available for the
             duration of the trial.

          5. Be ≥ 18 years of age on day of signing informed consent.

          6. Have a performance status of 0 or 1 on the ECOG Performance Scale.

          7. Demonstrate adequate organ function as defined in Table 1 of the protocol.

          8. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          9. Female subjects of childbearing potential (Section 6.5.2 - Contraception) must be
             willing to use an adequate method of contraception as outlined in Section 6.5.2 of the
             protocol - Contraception, for the course of the study through 120 days after the last
             dose of study medication.

             Note: Abstinence is acceptable if this is the usual lifestyle and preferred
             contraception for the subject.

         10. Male subjects of childbearing potential (Section 6.5.2- Contraception) must agree to
             use an adequate method of contraception as outlined in Section 6.5.2 of the protocol -
             Contraception, starting with the first dose of study therapy through 120 days after
             the last dose of study therapy.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          3. Has a known history of active TB (Bacillus Tuberculosis).

          4. Hypersensitivity to pembrolizumab or any of its excipients.

          5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent. Subjects with
             chronic conditions such as vision changes from plaque radiation therapy for ocular
             melanoma or prior hearing loss that is not reasonably expected to be exacerbated by
             the investigational product may be included.

             Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may
             qualify for the study.

             Note: If subject received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.

          7. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          8. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          9. Has known history of, or any evidence of active, non-infectious pneumonitis.

         10. Has an active infection requiring systemic therapy.

         11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         12. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         13. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         17. Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

         18. Has known sensitivity to retinoic acid derivatives.

         19. Has a medical history of allogenic stem cell transplant or received a solid organ
             transplant.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximally Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of the combination of pembrolizumab and All-Trans Retinoic Acid
Time Frame:5 years
Safety Issue:
Description:MTD is defined as the highest dose level with no more than 3 DLT reported in 6 DLT-evaluable subjects. A target toxicity rate of approximately 33% of all 24 patients will be used to establish the RP2D.

Secondary Outcome Measures

Measure:Dose-Limiting Toxicity (DLT) for the combined treatment of pembrolizumab and All-Trans Retinoic Acid for each patient
Time Frame:5 years
Safety Issue:
Description:Toxicity will be evaluated according to NCI CTCAE Version 4.0. A dose limiting toxicity (DLT) will be defined as any grade 3 or higher related to VESNOID and/or Pembrolizumab.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • Pembrolizumab
  • All-Trans Retinoic Acid

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