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

NCT ID: NCT02403778

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-17
• Study Completion Date: 2023-01-18

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.

Conditions

Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Ipilimumab

Intervention Type: DRUG

Ipilimumab is current standard of care treatment for melanoma.

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.

Group Type: EXPERIMENTAL

VESANOID

Intervention Type: 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).

Ipilimumab

Intervention Type: DRUG

Ipilimumab is current standard of care treatment for melanoma.

Interventions

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).

Intervention Type: DRUG

Ipilimumab

Ipilimumab is current standard of care treatment for melanoma.

Intervention Type: DRUG

Other Intervention Names

ATRA; Tretinoin; IPI

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin McCarter, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 30121453 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

14-0948.cc

Identifier Type: -

Identifier Source: org_study_id