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

NCT02403778 | Completed Phase 2 Results DMC

• 1 other identifier: 14-0948.cc
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Keywords

Melanoma; Malignant Melanoma

Outcome Measures

Primary Outcomes (3)

• Number of Adverse Events

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

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

• MDSC Frequency

  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.

  84 and 130 days following the first treatment

• MDSC Suppressive Function

  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.

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

Secondary Outcomes (2)

• Changes in the Frequency of Tumor-specific T Cell Responses

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

• Unresectable Stage III and STAGE IV

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

Study Arms (2)

Ipilimumab

ACTIVE COMPARATOR

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

VESANOID

EXPERIMENTAL

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; Drug: Ipilimumab

Interventions

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).

Also known as: ATRA, Tretinoin

VESANOID

Ipilimumab DRUG

Ipilimumab is current standard of care treatment for melanoma.

Also known as: IPI

Ipilimumab; VESANOID

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• 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.

  PMID: 30121453 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Tretinoin; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Martin McCarter
• Organization: Univesity Colorado Ansshutz Medical Campus

martin.mccarter@ucdenver.edu

303-724-2728

Study Officials

• Martin McCarter, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: March 31, 2015
• Study Start: December 17, 2015
• Primary Completion: August 1, 2018
• Study Completion: January 18, 2023
• Last Updated: September 21, 2023
• Results First Posted: July 16, 2019

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)