Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Dermatologic Agents

All Drugs and Chemicals

Tretinoin

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Keratolytic Agents

Patients will receive pembrolizumab infusions every three weeks. Patients will also receive 3 days of all-trans retinoic acid treatment surrounding each of the first 4 infusions of pembrolizumab, beginning one day prior to the infusion (a total of 12 days of all-trans retinoic acid).

All the patients will receive 200mg Q3W pembrolizumab treatment plus the supplemental treatment of 150 mg/m2 All-Trans Retinoic Acid orally for 3 days surrounding each of the first four infusions of pembrolizumab

Pembrolizumab with All-Trans Retinoic Acid

Martin McCarter, MD

This is a Phase I/Ib investigator-initiated open label of the combination of VESANOID and pembrolizumab treatment.

Primary Objective

* To identify the MTD and RP2D of the combination of pembrolizumab and ATRA.

Secondary Objective:

* Describe the safety and toxicity of combined treatment with pembrolizumab and all-trans retinoic acid (ATRA) \[brand name VESANOID\] in melanoma patients.
* To assess the anti-tumor activity in terms of a). The reduction in MDSC (immunosuppressive myeloid -derived suppressor cells) frequency and suppressive function (measured as a continuous variable)in peripheral blood of advanced melanoma patients undergoing pembrolizumab and VESANOID combination therapy. b). progression free survival.

Exploratory Objective

* To determine the clinical outcomes with tumor-specific T cell responses.

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

Pembrolizumab and All-Trans Retinoic Acid in Combination Treatment of Advanced Melanoma

MTD is defined as the highest dose level with no more than 3 DLTs reported in 6 DLT-evaluable subjects. A target toxicity rate of approximately 33% of all 24 patients will be used to establish the RP2D. This is one part of the pembrolizumab-ATRA combination treatment.

MTD is defined as the highest dose level with no more than 3 DLT reported in 6 DLT-evaluable subjects. A target toxicity rate of approximately 33% of all 24 patients will be used to establish the RP2D. This dose is one part of the pembrolizumab-ATRA combination treatment.

Toxicity is evaluated according to NCI CTCAE Version 4.0. A dose limiting toxicity (DLT) is defined as any grade 3 or higher adverse event related to VESNOID (the all-trans retinoic acid) and/or pembrolizumab.

Progression free survival was calculated from treatment start date to data cutoff date.

Anti-tumor activity will be determined by the percent change in MDSC (immunosuppressive myeloid-derived suppressor cells) frequency in peripheral blood of advanced melanoma patients undergoing the combined treatment of pembrolizumab and All-Trans Retinoic Acid (ATRA). Pre-treatment levels will be compared to post-treatment levels, where post-treatment means 4-6 weeks after stopping ATRA. MDSCs include CD45+, CD3-, CD19-, CD56-, CD11b+, CD33+, and HLA-DR-/low.

In the original protocol, suppressive function was included as part of this outcome measure to assess anti-tumor activity. However, this analysis could not be performed because the decrease in concentration of MDSCs after treatment resulted in inadequate data for the planned assays.

Merck Sharp & Dohme LLC

University of Colorado, Denver

Patients will receive pembrolizumab infusions every three weeks. Patients will also receive 3 days of all-trans retinoic acid treatment surrounding each of the first 4 infusions of pembrolizumab, beginning one day prior to the infusion (a total of 12 days of all-trans retinoic acid).

Pembrolizumab with All-Trans Retinoic Acid: All the patients will receive 200mg Q3W pembrolizumab treatment plus the supplemental treatment of 150 mg/m2 All-Trans Retinoic Acid orally for 3 days surrounding each of the first four infusions of pembrolizumab

Pembrolizumab With All-Trans Retinoic Acid

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Martin McCarter

The analysis population is 24 patients rather than 25 because one patient was not on treatment long enough to be evaluated for any outcomes.

Maximally Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Pembrolizumab

Number of Patients With a Dose-Limiting Toxicity (DLT) for the Combined Treatment of Pembrolizumab and All-Trans Retinoic Acid

Progression Free Survival

Responding patients

Non-responding patients

Overall

Percent change in MDSC was computed both in total and separately for i) patients that responded to therapy, and ii) patients that did not respond to therapy. Response was evaluated using RECIST v1.1 criteria. The analysis population for this outcome measure is 23 patients because one patient did not complete a post-treatment blood draw.

Percent Change in Anti-Tumor Activity

Maximally Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of All-Trans Retinoic Acid

Overall Study

Spots Global Cancer Trial Database for Pembrolizumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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