Highlights of the NCCN Oncology Research Program

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.

For more information on specific trials, including patient selection criteria, use the contact information listed with each study.

For more information on the NCCN ORP, including a complete detailing of the clinical studies currently underway at NCCN Member Institutions, go to www.nccn.org/education-research/nccn-oncology-research-program/orp-main-page.

A Phase 1b Clinical Trial: Improving Outcomes With Androgen Pathway Inhibitors by Targeting DNA Methyltransferase Activity

Principal Investigator: Gurkamal S. Chatta, MD

Condition: Metastatic castration-resistant prostate cancer

Institution: Roswell Park Comprehensive Cancer Center

This phase Ib clinical trial seeks to determine the best dose of decitabine/cedazuridine and possible benefits and/or adverse effects of decitabine/cedazuridine and enzalutamide in treating patients with metastatic castration-resistant prostate cancer (mCRPC). Epigenetic drugs, such as decitabine/cedazuridine, work in different ways to stop the growth of tumor cells, either by stopping them from dividing or by making them more susceptible to enzalutamide. Enzalutamide blocks the use of androgen by the tumor cells. Giving decitabine/cedazuridine together with enzalutamide may reverse or help prevent the acquired therapeutic resistance that is observed when enzalutamide is used alone. Drug resistance occurs when cancer cells stop responding to a drug that had previously been effective.

Primary Objective:

  • Determine the safety of oral decitabine and cedazuridine (decitabine/cedazuridine) in combination with enzalutamide in patients with mCRPC

Secondary Objective:

  • Determine the maximum tolerated dose and recommended phase II dose of oral decitabine/cedazuridine in combination with enzalutamide in patients with mCRPC

Exploratory Objectives:

  • Determine the relationship between decitabine/cedazuridine dose and plasma biomarkers such as HbF and LINE-1 methylation

  • Analyze circulating tumor DNA by whole-exome sequencing and DNA methylation analysis to monitor effects of treatment and emergence of androgen receptor–low CRPC/neuroendocrine prostate cancer

  • Measure the intended molecular pharmacodynamic effects of DNA methyltransferase-1 (DNMT1) depletion (ie, LINE-1 demethylation in tumor tissue)

  • Assess effects of treatment on tumor cell DNA methylation using Infinium MethylationEPIC arrays where suitable tissue is accessible

  • Evaluate drug exposure to decitabine/cedazuridine by pharmacokinetic sampling on day 3, 4, or 5 (cohorts –1, 1, 2) of cycle 1

Contact: Gurkamal Chatta, MD • 716-845-3117 • Gurkamal.Chatta@roswellpark.org

ClinicalTrials.gov Identifier: NCT05037500

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