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Trial record 12 of 2206 for:    Melanoma

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

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ClinicalTrials.gov Identifier: NCT02403778
Recruitment Status : Active, not recruiting
First Posted : March 31, 2015
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: VESANOID Drug: Ipilimumab Phase 2

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
Actual Study Start Date : December 17, 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Active Comparator: Ipilimumab
Arm A (No VESANOIDTherapy) will receive the standard of care treatment with ipilimumab only, receiving the standard 4 doses of either 3 or 10 mg/kg ipilimumab every 3 weeks.
Drug: Ipilimumab
Ipilimumab is current standard of care treatment for melanoma.
Other Name: IPI

Experimental: VESANOID
Arm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment.
Drug: VESANOID
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

Drug: Ipilimumab
Ipilimumab is current standard of care treatment for melanoma.
Other Name: IPI




Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: Study start to study end date, up to 2 years. ]
    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: Study start to study end date, up to 2 years. ]
    The reduction in MDSC frequency and suppressive function in peripheral blood of advanced melanoma patients undergoing ipilimumab and VESANOID combination therapy by flow cytometry..

  3. MDSC suppressive function [ Time Frame: Study start to study end date, up to 2 years. ]
    MDSC suppressive function in peripheral blood of Stage IV melanoma patients will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs.


Secondary Outcome Measures :
  1. Changes in the frequency of tumor-specific T cell responses [ Time Frame: Study start to study end date, up to 2 years. ]
    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: Study start to study end date, up to 2 years. ]
    Subjects will be followed for RECIST 1.1



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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02403778


Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Martin McCarter, MD University of Colorado, Denver

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02403778     History of Changes
Other Study ID Numbers: 14-0948.cc
First Posted: March 31, 2015    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of Colorado, Denver:
Melanoma
Malignant Melanoma

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Antibodies, Monoclonal
Tretinoin
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Keratolytic Agents
Dermatologic Agents