The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program’s establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.
NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.
This feature highlights an NCCN study funded through the grant mechanism.
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
Principal Investigator: Martin McCarter, MD
Condition: Unresectable or metastatic mucosal melanoma
Institution: University of Colorado Cancer Center
This is a phase Ib/II, investigator-initiated, open-label trial of the combination of oral decitabine/cedazuridine (DEC-C) and nivolumab treatment. This single-center study will be conducted at the University of Colorado Cancer Center (UCHealth central campus).
Bayesian optimal interval (BOIN) design will be used to assess the recommended phase II dose (RP2D) during phase Ib. The BOIN design is a model assistant approach used in phase I clinical trials for finding the maximum tolerated dose (MTD). The investigators anticipate 7 to 12 patients will be treated at the RP2D in phase Ib dose de-escalation, and consider that as the first stage. If there is at least one response among these patients, the trial will proceed to the second stage and enroll additional patients to reach a minimum of 16 patients.
The objective of phase II is to preliminarily evaluate 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 Ib will be included in analysis for the phase II component of this study. All patients enrolled at the RP2D level and receiving at least 2 treatment cycles will be included in the efficacy and safety/tolerability endpoint analysis. Our results indicate that the objective response rate (ORR) to anti–PD-1 in patients with mucosal melanoma at our institution is 8%. The investigators hypothesize that the ORR for the combination will be 33%—a 25% absolute improvement over the anti–PD-1 treatment. Simon’s 2-stage design will be used to evaluate the ORRs. The null hypothesis that the ORR is 8% will be rejected if there are ≥4 responses among the 16 patients. The design yields a type I error rate of 0.032 and power of 80% when the true response rate is 33%. The total sample size required for phase II will depend on the number of patients treated at the RP2D during phase Ib, and it is estimated that the total sample size will be in the range of 16 to 21 patients.
• Establish the safety and tolerability of DEC-C in combination with nivolumab in patients with unresectable, locally advanced, or metastatic mucosal melanoma
• Determine the response rate to DEC-C in combination with nivolumab in patients with unresectable, locally advanced, or metastatic mucosal melanoma
• Determine whether the addition of DEC-C to nivolumab increases progression-free survival and overall survival in patients with unresectable, locally advanced, or metastatic mucosal melanoma
• Evaluate the effect of DEC-C in combination with nivolumab on circulating and tumor immune cell profiles
• Determine the effect of DEC-C in combination with nivolumab on global hypomethylation and RIG-I pathway gene expression in circulating cells and tumor cells
• Determine the effect of DEC-C in combination with nivolumab on circulating and tumor innate immune sensing cytokines and proteins