A Mass Balance Study of [14C]-Nanatinostat and Relative Bioavailability Study of Nanatinostat in Patients With Advanced Cancers

A Phase 1 Study to Investigate the Mass Balance of [14C]-Nanatinostat and to Evaluate the Relative Bioavailability of Nanatinostat in Patients With Selected Advanced Cancers

This study will determine how nanatinostat is absorbed, modified, and removed from the body (Part A), the amount of nanatinostat that becomes available to the body (Part B), and will evaluate the safety and tolerability of nanatinostat (Part C) in patients with advanced cancers.

Study Overview

• Status: Recruiting
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: [14C]-Nanatinostat; Drug: Nanatinostat (free base) tablets in combination with Valganciclovir; Drug: Nanatinostat mesylate tablets in combination with Valganciclovir; Drug: Single-agent Nanatinostat (free base) tablets

Detailed Description

This is a Phase 1, open-label, 3-part study evaluating the mass balance, pharmacokinetics, and metabolism of nanatinostat following a single oral dose of [14C]-nanatinostat for Part A, evaluating relative bioavailability of nanatinostat mesylate and nanatinostat (free base) tablets after coadministration with valganciclovir in patients with advanced stage cancers for Part B, and evaluating the safety and antitumor activity of nanatinostat for Part C.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Afton Katkov, MSc; Phone Number: 858-400-8470; Email: ClinicalTrials@Viracta.com

Study Locations

• Spain
  • Madrid, Spain, 28050
    • Recruiting
    • START Madrid - CIOCC - Hospital Universitario HM Sanchinarro
    • Contact: Email: ClinicalTrials@Viracta.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Have histologically confirmed advanced stage cancers (excluding gastrointestinal tumors), have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment, and have no available treatment with curative intent.
• Eastern Cooperative Oncology Group Performance Status of ≤2 at Screening.
• Body mass index ≥18.5 but ≤30.0 kg/m2 at Screening.
• Adequate bone marrow, liver, and kidney function.

Key Exclusion Criteria:

• Presence of active central nervous system and/or leptomeningeal disease.
• Anticancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy, or use of other investigational agents within 4 weeks before study entry.
• Inability to take or tolerate oral medication.
• Any gastrointestinal, liver, or kidney condition that may affect drug absorption and metabolism.
• Active infection requiring systemic therapy.
• Has received radiolabeled material <12 months (excluding that required for imaging) prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: [14C]-Nanatinostat	Drug: [14C]-Nanatinostat; A single oral dose administered on Day 1 in a fasted state.
Experimental: Part B (Treatment A): Nanatinostat (free base) tablets in combination with Valganciclovir; Patients will be randomized into 2 treatment sequences (AB and BA) in Periods 1 and 2. Each treatment period is 24 hours.	Drug: Nanatinostat (free base) tablets in combination with Valganciclovir; Treatment A: a single, oral dose of nanatinostat (free base) tablets (20 mg) in combination with valganciclovir (900 mg) under fed conditions.
Experimental: Part B (Treatment B): Nanatinostat mesylate tablets in combination with Valganciclovir; Patients will be randomized into 2 treatment sequences (AB and BA) in Periods 1 and 2. Each treatment period is 24 hours.	Drug: Nanatinostat mesylate tablets in combination with Valganciclovir; Treatment B: a single, oral dose of nanatinostat mesylate tablets (20 mg) in combination with valganciclovir (900 mg) under fed conditions.
Experimental: Part C: Single-agent Nanatinostat (free base) tablets	Drug: Single-agent Nanatinostat (free base) tablets; 40 mg once daily under fed conditions until disease progression or unacceptable toxicity, whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The amount of radioactivity in excreta [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: area under the plasma concentration versus time curve (AUC) [Part B]	8 weeks after the last discharge visit in Part B
Pharmacokinetic Parameter: maximum plasma concentration (Cmax) [Part B]	8 weeks after the last discharge visit in Part B
Pharmacokinetic Parameter: time to maximum observed plasma concentration (Tmax) [Part B]	8 weeks after the last discharge visit in Part B
Pharmacokinetic Parameter: Fraction of the administered dose in comparison with a standard (Frel) [Part B]	8 weeks after the last discharge visit in Part B
Incidence of adverse events and serious adverse events [Part C]	28 days after the last dose of study treatment in Part C

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and serious adverse events [Parts A and B]	Up to 7 days after the last discharge visit
Incidence of clinically significant changes in selected safety assessments [Parts A and B]	Up to 7 days after the last discharge visit
Pharmacokinetic Parameter: area under the plasma concentration versus time curve (AUC) [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: maximum plasma concentration (Cmax) [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: time to maximum observed plasma concentration (Tmax) [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: elimination half-life (t1/2) [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: apparent total clearance (CL/F) [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: apparent volume of distribution during terminal phase (Vz/F) [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: elimination rate constant from the central compartment (Kel) [Part A]	8 weeks after the last discharge visit in Part A
The ratio of total radioactivity in blood relative to plasma [Part A]	8 weeks after the last discharge visit in Part A
[14C]-metabolic profile and identification of metabolites in plasma [Part A]	8 weeks after the last discharge visit in Part A
Major radioactive peak/metabolites in urine and fecal radiochromatograms as a percentage of the radioactive dose [Part A]	8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: elimination half-life (t1/2) [Part B]	8 weeks after the last discharge visit in Part B
Pharmacokinetic Parameter: metabolite-to-parent ratio [Part B]	8 weeks after the last discharge visit in Part B
Objective Response Rate (ORR) [Part C]	Approximately 1 year
Time to Response (TTR) [Part C]	Approximately 1 year
Duration of Response (DOR) [Part C]	Approximately 1 year
Disease Control Rate (DCR) [Part C]	Approximately 1 year

Collaborators and Investigators

• Sponsor: Viracta Therapeutics, Inc.
• Investigators: Study Director: Darrel P Cohen, MD, PhD, Viracta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: VT3996-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes