NCT05089370

Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab for Patients With Mucosal Melanoma

Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab as a Strategy to Enhance the Efficacy of Immune Checkpoint Blockade in Unresectable or Metastatic Mucosal Melanoma

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes by DEC-C during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells. This may increase the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit patients with mucosal melanoma.

Detailed description

This is a Phase Ib/II investigator-initiated open label trial of the combination of DEC-C and Nivolumab treatment. This is a single-center study to be conducted at the University of Colorado Cancer Center (UCHealth central campus). A complete and current listing of investigators, research personnel, and research facilities participating in this study will be maintained throughout the duration of this study on applicable study required forms such as an FDA Form 1572, the COMIRB Research Personnel Form, and/or a UCCC Protocol Contact List, incorporated herein by reference. Phase Ib: A time-to-event Bayesian optimal interval (TITE-BOIN) design will be used to assess the RP2D during phase 1b. The BOIN design is a model assistant approach used in phase I clinical trials for finding the maximum tolerated dose (MTD). The Investigator anticipates a maximum of 9 patients treated at the RP2D in Phase 1b dose de-escalation and considers as subjects in stage 1 of phase 2. Phase II: The objective of Phase II is to preliminarily evaluate the efficacy and further evaluate safety of the combination at the RP2D. The phase II cohort will enroll patients using the established RP2D of DEC-C from the phase Ib portion in combination with standard doses of Nivolumab. Patients treated at the RP2D in Phase 1b will be included in analysis for the Phase II component of this study. All patients enrolled at the RP2D level and receiving any DEC-C treatment will be included in the efficacy and safety/tolerability endpoint analysis. The results indicate that the objective response rate (ORR) to anti-PD1 in mucosal melanoma patients at our institution is 20%. The Investigator hypothesizes ORR for the combination will be 43%, a 23% absolute improvement over the anti-PD1 treatment. Simon's 2-stage design will be used to evaluate the ORRs. The null hypothesis that the ORR is 20% will be rejected if there are 3 or more responses among the 11 patients (including phase Ib RP2D patients). The design yields a type I error rate of 001 and power of 80% when the true response rate is 43%. The total sample size required for the Phase II will depend on the number of patients treated at the RP2D during Phase 1b, and it is estimated the total sample size will be in the range of 19-21 subjects.

Conditions

• Malignant Melanoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab	Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells (MDSCs, Tregs) (1-4), increasing the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit mucosal melanoma patients.

Timeline

• Start date: 2022-06-20
• Primary completion: 2026-08-31
• Completion: 2026-10-01
• First posted: 2021-10-22
• Last updated: 2025-12-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study