Advanced Cancer
Conditions
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.
Interventions
DRUG[14C]-Nanatinostat
A single oral dose administered on Day 1 in a fasted state.
DRUGNanatinostat (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.
DRUGNanatinostat 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.
DRUGSingle-agent Nanatinostat (free base) tablets
40 mg once daily under fed conditions until disease progression or unacceptable toxicity, whichever occurs first.
Sponsors
Viracta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This clinical trial is divided into 3 parts (Part A, Part B, and Part C). Patients may begin their study participation in Part A or Part B. Part B (for patients who participate in Part A) and Part C (for patients who participate in Part A and/or Part B) are optional for patients who meet certain conditions for crossover. In Part A, patients will be given a single dose of radiolabeled nanatinostat by mouth on Day 1. Patients may stay in the hospital up to 8 days. In Part B, patients will receive both nanatinostat in a salt form and a non-salt form, coadministered with valganciclovir in different order across 2 treatment days. Patients will be randomly assigned to either receive the salt or the non-salt form of nanatinostat first. Patients may stay in the hospital up to 4 days. Part C will allow patients to continue receiving nanatinostat treatment as long as they are deriving clinical benefit. This part will not require a hospital stay.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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: area under the plasma concentration versus time curve (AUC) [Part A] | 8 weeks after the last discharge visit in Part A |
| 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 |
| Pharmacokinetic Parameter: elimination half-life (t1/2) [Part B] | 8 weeks after the last discharge visit in Part B |
| Pharmacokinetic Parameter: maximum plasma concentration (Cmax) [Part A] | 8 weeks after the last discharge visit in Part A |
| Incidence of clinically significant changes in selected safety assessments [Parts A and B] | Up to 7 days after the last discharge visit |
| Incidence of adverse events and serious adverse events [Parts A and B] | Up to 7 days after the last discharge visit |
| 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 |
Countries
Spain
Outcome results
None listed