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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 2

Conditions: Melanoma

Treatments: Drug: Ipilimumab; Drug: VESANOID

Study type: Interventional

Funder types: Other

Identifiers

NCT02403778

14-0948.cc

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 89 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

Ipilimumab

Active Comparator group

Description:

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.

Treatment:

Drug: Ipilimumab

VESANOID

Experimental group

Description:

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.

Treatment:

Drug: VESANOID

Drug: Ipilimumab