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

NCT03200847 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 16-1080.ccPMID 36378549
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Stage IV Melanoma; Stage III Melanoma; Advanced Melanoma

Keywords

Pembrolizumab; All-Trans Retinoic Acid

Outcome Measures

Primary Outcomes (2)

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

  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.

  21 days from first dose of combined treatment

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

  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.

  21 days from first dose of combined treatment

Secondary Outcomes (3)

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

  2 years

• Progression Free Survival

  up to 36 months

• Percent Change in Anti-Tumor Activity

  Pre-treatment (0-30 days before first ATRA administration) and post-treatment (84-130 days after first ATRA administration)

Study Arms (1)

Pembrolizumab with All-Trans Retinoic Acid

EXPERIMENTAL

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).

Drug: Pembrolizumab with All-Trans Retinoic Acid

Interventions

Pembrolizumab with All-Trans Retinoic Acid DRUG

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

Also known as: VESANOID, Keytruda

Pembrolizumab with All-Trans Retinoic Acid

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of advanced melanoma (unresectable Stage III or Stage IV Melanoma).
• Planned standard treatment with pembrolizumab.
• Be willing and able to provide written informed consent for the trial.
• State willingness to comply with all study procedures and be available for the duration of the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1 of the protocol.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 6.5.2 - Contraception) must be willing to use an adequate method of contraception as outlined in Section 6.5.2 of the protocol - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 6.5.2- Contraception) must agree to use an adequate method of contraception as outlined in Section 6.5.2 of the protocol - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Subjects with chronic conditions such as vision changes from plaque radiation therapy for ocular melanoma or prior hearing loss that is not reasonably expected to be exacerbated by the investigational product may be included.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80528, United States

Location

Related Publications (1)

• Tobin RP, Cogswell DT, Cates VM, Davis DM, Borgers JSW, Van Gulick RJ, Katsnelson E, Couts KL, Jordan KR, Gao D, Davila E, Medina TM, Lewis KD, Gonzalez R, McFarland RW, Robinson WA, McCarter MD. Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma. Clin Cancer Res. 2023 Apr 3;29(7):1209-1219. doi: 10.1158/1078-0432.CCR-22-2495.

  PMID: 36378549 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Tretinoin

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

Results Point of Contact

• Title: Dr. Martin McCarter
• Organization: University of Colorado Hospital

martin.mccarter@cuanschutz.edu

13037242725

Study Officials

• Martin McCarter, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: June 27, 2017
• Study Start: October 31, 2017
• Primary Completion: July 20, 2022
• Study Completion: October 19, 2022
• Last Updated: October 1, 2024
• Results First Posted: March 2, 2023

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)