Clinical trial NCT02403778: Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
Official title: Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: Melanoma
Malignant Melanoma
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-03-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Adverse Events
timeFrame: Up to 2 years from the time of study enrollment for each patient.
measure: MDSC Frequency
timeFrame: 84 and 130 days following the first treatment
measure: MDSC Suppressive Function
timeFrame: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
Secondary outcomes:
measure: Changes in the Frequency of Tumor-specific T Cell Responses
timeFrame: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
measure: Unresectable Stage III and STAGE IV
timeFrame: Up to 2 years from the time of study enrollment for each patient.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Martin McCarter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tobin RP, Jordan KR, Robinson WA, Davis D, Borges VF, Gonzalez R, Lewis KD, McCarter MD. Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab. Int Immunopharmacol. 2018 Oct;63:282-291. doi: 10.1016/j.intimp.2018.08.007. Epub 2018 Aug 16.