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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Viracta Therapeutics, Inc.
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Pharmacokinetic Parameter: Fraction of the administered dose in comparison with a standard (Frel) [Part B]
Study Overview
Brief Summary
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.
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.
The study was terminated prematurely and did not reach its target enrollment.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Arms & Interventions
Part A: [14C]-Nanatinostat
Intervention: [14C]-Nanatinostat (Drug)
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.
Intervention: Nanatinostat (free base) tablets in combination with Valganciclovir (Drug)
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.
Intervention: Nanatinostat mesylate tablets in combination with Valganciclovir (Drug)
Part C: Single-agent Nanatinostat (free base) tablets
Intervention: Single-agent Nanatinostat (free base) tablets (Drug)
Outcomes
Primary Outcomes
Pharmacokinetic Parameter: Fraction of the administered dose in comparison with a standard (Frel) [Part B]
Time Frame: 8 weeks after the last discharge visit in Part B
The amount of radioactivity in excreta [Part A]
Time Frame: 8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: area under the plasma concentration versus time curve (AUC) [Part B]
Time Frame: 8 weeks after the last discharge visit in Part B
Pharmacokinetic Parameter: maximum plasma concentration (Cmax) [Part B]
Time Frame: 8 weeks after the last discharge visit in Part B
Incidence of adverse events and serious adverse events [Part C]
Time Frame: 28 days after the last dose of study treatment in Part C
Pharmacokinetic Parameter: time to maximum observed plasma concentration (Tmax) [Part B]
Time Frame: 8 weeks after the last discharge visit in Part B
Secondary Outcomes
- Duration of Response (DOR) [Part C](Approximately 1 year)
- Disease Control Rate (DCR) [Part C](Approximately 1 year)
- 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)
- Time to Response (TTR) [Part C](Approximately 1 year)
- 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: 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)
- 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)
- The ratio of total radioactivity in blood relative to plasma [Part A](8 weeks after the last discharge visit in Part A)
- 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: 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)
- [14C]-metabolic profile and identification of metabolites in plasma [Part A](8 weeks after the last discharge visit in Part A)
- Objective Response Rate (ORR) [Part C](Approximately 1 year)