Primary objective:• To assess the mass balance of nanatinostat (ie, evaluate clearance mechanisms of nanatinostat and drug-related metabolites) following a single oral dose of [14C]-nanatinostat in patients with advanced cancer.Secondary objectives…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints
• The amount of radioactivity excreted in urine and feces with an objective to
recover >=90% of the radiolabeled nanatinostat.
Secondary outcome
Secondary:
• Concentration-time profile and PK parameters of total radioactivity from
analysis of plasma, urine, and feces collected at identified timepoints.
• PK parameter estimates for nanatinostat and metabolites M1 and M2 in plasma.
• The amount of radioactivity in plasma and whole blood, including the
erythrocyte transfer ratio (ETR) and erythrocyte/plasma partition coefficient
(EPPC).
• [14C]-metabolic profile and identification of metabolites in plasma and/or
blood
• Major radioactive peak/metabolites in the urine and fecal radiochromatograms
as a percentage of the radioactive dose.
• Incidence and severity of treatment-emergent adverse events (TEAEs). Adverse
events (AEs) will be graded according to National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Background summary
Nanatinostat (also known as VRx-3996 and CHR-3996) is an orally administered
hydroxamic acid-based, class-I selective histone deacetylase (HDAC) inhibitor
that is currently in development in combination with the antiviral drug
valganciclovir for the treatment of patients with advanced Epstein-Barr virus
(EBV)-associated malignancies.
The safety, tolerability and pharmacokinetics (PK) of nanatinostat were
initially evaluated in a Phase 1 dose-escalation safety trial in 39 patients
with advanced solid tumors. Nanatinostat was generally well-tolerated, and
preliminary clinical activity was shown; a partial response was seen in one
patient with metastatic acinar pancreatic carcinoma, and 9 patients had a best
response of stable disease.
The combination of nanatinostat and valganciclovir (VALCYTE®), an oral prodrug
of ganciclovir, is currently under investigation in 3 ongoing studies including
a Phase 1b/2 study (VT3996-201) in patients with relapsed/refractory
EBV-positive (EBV+) lymphoma, a Phase 2 study (VT3996-202) in patients with
EBV+ relapsed/refractory lymphomas, and a Phase 1b/2 study (VT3996-301) in
patients with advanced EBV+ solid tumors.
Study objective
Primary objective:
• To assess the mass balance of nanatinostat (ie, evaluate clearance mechanisms
of nanatinostat and drug-related metabolites) following a single oral dose of
[14C]-nanatinostat in patients with advanced cancer.
Secondary objectives:
• To evaluate the pharmacokinetics (PK) of nanatinostat and metabolites M1
(NT-IM-1, hydrolysis product) and M2 (NT-IM-2, N-hydroxyl reduction product) in
plasma.
• To screen and identify for profiling purposes potential nanatinostat
metabolites in selected and pooled plasma, feces, and urine samples.
• To assess safety and tolerability of [14C]-nanatinostat in patients with
advanced cancer.
Study design
This is a Phase 1, single-center, open-label, mass balance study.
Intervention
radiolabeled nanatinostat: [14C]-Nanatinostat
Study burden and risks
The proposed clinical trial is a human mass balance study of an investigational
medicinal product belonging to the well characterized class of HDAC inhibitors.
The risks associated with HDAC inhibitors are considered ethically acceptable
in the proposed study population, patients with metastatic or advanced solid
tumors refractory to standard therapy, albeit a potential treatment benefit is
unlikely after a single dose of nanatinostat monotherapy.
The overall risk assessments are acceptable in this patient population with the
dose level of 40 mg oral dose of nanatinostat, containing 88 µCi
[14C]-nanatinostat, given the available clinical data and with the supervision
and medical monitoring of participants during the study period in the unit.
Nanatinostat has been in clinical development as a monotherapy as well as in
combination, is oral, and over 100 patients have been dosed with this drug, and
thus its safety profile is well-established. Further, it is tolerated at much
larger daily doses with nearly all toxicities being reversible given its short
half-life, thus carrying little risk in a single-dose study. Results from this
phase 1 study will support further development of new therapies for cancer
patients who may not have other options for therapy at the present.
S. Coast Hwy 101, Suite 210 2533
Cardiff CA92007
US
S. Coast Hwy 101, Suite 210 2533
Cardiff CA92007
US
Listed location countries
Age
Inclusion criteria
1. Men or women that are at least 18 years of age at the time of informed
consent.
2. Has histologically confirmed metastatic or advanced solid tumors refractory
to standard therapy, and for whom no standard curative therapy exists.
3. Eastern Cooperative Oncology Group (ECOG) performance status: 0-2.
4. Adequate laboratory parameters (in absence of transfusion support within
three weeks or growth factor within two weeks of Screening), including:
Absolute neutrophil count (ANC) >=1500/mm3 = 1.5 × 109/L.
Platelets count >=90,000/mm3 = 90 × 109/L.
Hemoglobin >=9.0 g/dL.
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <=2.5 × upper
limit of normal (ULN), or < 5x ULN in the presence of liver metastases.
Total bilirubin <=1.5 × ULN unless considered due to Gilbert*s syndrome, in
which case, <=3.0 × ULN.
Estimated glomerular filtration rate (eGFR) >=60 mL/min by CKD-EPI equation.
Serum potassium, magnesium, and corrected calcium outside normal limits for
institution that are assessed as clinically significant by the Investigator
should be treated to correct abnormalities with confirmation on repeat lab
studies.
5. Life expectancy >3 months, as determined by the treating physician.
Exclusion criteria
1. Known history of central nervous system and/or leptomeningeal disease.
2. Prior treatment with [14C]-nanatinostat or history of allergic reactions
attributed to compounds
of similar chemical or biologic composition to [14C]-nanatinostat.
3. Inability to take or tolerate oral medication.
4. Any gastrointestinal, liver, or kidney condition that may affect drug
absorption and metabolism.
5.Is currently participating in or has participated in an interventional study
of an investigational agent or has used an investigational device within 4
weeks or 5 half-lives prior to dosing, whichever is longer.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-001630-11-NL |
| CCMO | NL81579.056.22 |