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NCT Number: NCT02403778

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

The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients.

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Key information

Conditions

Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year–89 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

About this study

The successful treatment of melanoma with immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) antibodies, has altered our thinking and approach to immunotherapy for solid tumors. Despite these advances, only a portion of patients experience a durable response suggesting that there is room for improvement via enhanced immunomodulatory approaches. Anti-CTLA-4 (Ipilimumab) significantly improves overall survival and achieves long-lasting complete responses in some melanoma patients, the number of patients that achieve durable clinical benefit is limited and could be improved by a combined immunomodulatory approach. The objectives of this study are to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. We hypothesize that combined treatment with Ipilimumab and ATRA will improve patient responses, increase tumor antigen-specific T cell responses, and decrease immunosuppressive myeloid-derived suppressor cells (MDSCs) in melanoma patients compared to patients treated with Ipilimumab alone.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients over the age of 18 year.
  • Patients diagnosed with advanced melanoma.
  • Patients that are considered candidates for ipilimumab therapy.
  • Patients able to understand and willing to sign a written informed consent documents.
  • Patients willing to have regular blood draws, one before treatment and four during or after treatment.

Exclusion criteria

  • Patients under the age of 18.
  • Patients with Stage I or II, melanoma who are not candidates for Ipilimumab.
  • Patients that have received systemic treatments within four weeks prior to the beginning of treatment.
  • Women that are pregnant or nursing.
  • Patients taking immunosuppressive medications.
  • Patients with active autoimmune disease.
  • Patients with known sensitivity to retinoic acid derivatives.
  • Patients with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin > 2.5 × ULN.

Treatment and study plan

VESANOID

Drug

All-trans retinoic acid (ATRA) is a vitamin A derivative that binds the retinoic acid receptor on MDSCs and differentiates immature monocytes into more mature dendritic cells (12). VESANOID is a standard treatment for patients with acute promyelocytic leukemia (APL).

Other names: ATRA, Tretinoin

Ipilimumab

Drug

Ipilimumab is current standard of care treatment for melanoma.

Other names: IPI

Primary outcomes

  1. Number of Adverse Events

    Time frame: Up to 2 years from the time of study enrollment for each patient.

    Safety and tolerability of ipilimumab and VESANOID combination therapy in advanced melanoma patients will be established using the Bayesian approach.

  2. MDSC Frequency

    Time frame: 84 and 130 days following the first treatment

    The frequency of circulating MDSCs will be measured by flow cytometry and calculated as a percentage of the total myeloid cell population. This outcome will be measured at the final study blood draw between 84 and 130 days following the first treatment.

  3. MDSC Suppressive Function

    Time frame: 4 weeks prior to start, Midway thru and at least 30 days post final infusion

    MDSC suppressive function in peripheral blood will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs. Functional assays will be performed to assess the ability of isolated MDSCs to suppress T-cell responses.

Secondary outcomes

  1. Changes in the Frequency of Tumor-specific T Cell Responses

    Time frame: 4 weeks prior to start, Midway thru and at least 30 days post final infusion

    Changes in the frequency of tumor-specific T cell responses attributable to the addition of VESANOID to standard ipilimumab therapy will be determined by the frequency of Interferons (IFN)-gamma producing cells after stimulation with melanoma antigens.

  2. Unresectable Stage III and STAGE IV

    Time frame: Up to 2 years from the time of study enrollment for each patient.

    Subjects will be followed for evidence of disease progression.

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Registry information

Important dates

Study start
2015
Primary completion
2018
Study completion
2023
First posted
Mar 31, 2015
Registry last updated
Sep 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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