A Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics of PV-10 Chemoablation of Cancer Metastatic to the Liver or Recurrent Hepatocellular Carcinoma Not Amenable to Resection or Transplant
Subject will be enrolled in one of three planned cohorts (Main Study Group, Expansion Cohort
1 or Expansion Cohort 2).
Main Study Group. Three initial subjects with either recurrent HCC or cancer metastatic to
the liver will receive 0.25 mL PV-10 per cc lesion volume (Lv) to a single lesion (up to a
maximum dose of 7.5 mL PV-10). If none of the initial three subjects experiences a new and
persistent CTCAE Grade 3 or greater non-hematological or any Grade 4 hematological toxicity
over a 28-day follow-up interval, an additional three subjects will be enrolled and
similarly treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15
mL PV-10) provided no new and persistent Grade 3 or greater non-hematological or any Grade 4
hematological toxicity occurs.
Expansion Cohort 1 (EC1). Following demonstration of safety and tolerability in the Main
Study Group, up to 24 additional subjects with cancers metastatic to the liver or with
recurrent HCC will be enrolled into this expansion cohort. Subjects will be treated with
PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10). Enrollment
will continue provided no new and persistent Grade 3 or greater non-hematological (excluding
fatigue) or any Grade 4 hematological toxicity occurs.
Expansion Cohort 2 (PV-10 plus Sorafenib). Following demonstration of safety and
tolerability in the Main Study Group, up to 6 additional subjects with HCC receiving
sorafenib at a dose that has been stable and tolerable for at least 4 weeks will be enrolled
into each of two successive dose groups in Expansion Cohort 2.
The first 3 subjects will be assigned to Expansion Cohort 2.1 (EC2.1) and will receive PV-10
administered at 0.25 mL PV-10 per cc Lv (up to a maximum dose of 7.5 mL PV-10). If none of
the initial 3 subjects experiences dose-limiting toxicity (DLT), defined as onset of any
Grade 3 or greater non-hematological (excluding fatigue) or Grade 4 hematological toxicity
within 28 days of PV-10 administration that is persistent for 14 days or longer, enrollment
in Expansion Cohort 2.2 will commence. If 2 or more of the initial 3 subjects experience a
DLT, the combination of PV-10 and sorafenib at this PV-10 dose level will be judged to be
intolerable. If one of the initial 3 subjects experiences a DLT, an additional 3 subjects
will be enrolled in Expansion Cohort 2.1. If none of these additional subjects experiences a
DLT, enrollment in Expansion Cohort 2.2 will commence. If 1 or more of the 3 additional
subjects (i.e., ≥ 2 of 6 subjects) experiences a DLT, the combination of PV-10 and sorafenib
at this PV-10 dose level will be judged to be intolerable.
If Expansion Cohort 2.1 has been completed with tolerable toxicity, enrollment in Expansion
Cohort 2.2 (EC2.2) will commence at a dose of 0.5 mL PV-10 per cc Lv (up to a maximum dose
of 15 mL PV-10). If none or 1 of the first 3 subjects enrolled experiences a DLT, the cohort
will be expanded to 6 subjects. If no more than 1 subject among 6 experiences a DLT, the
dose of 0.5 mL PV-10 per cc Lv will be judged to be the maximum tolerable dose (MTD) for the
study. If 2 or more of the 6 subjects experiences a DLT, the combination of PV-10 and
sorafenib at this PV-10 dose level will be judged to be intolerable.
If the Expansion Cohort 2.2 dose is not tolerated, Expansion Cohort 2.1 will be expanded to
6 subjects, unless this has already occurred. If more than 1 subject of the 6 experiences a
DLT, the Expansion Cohort 2.1 dose of PV-10 plus sorafenib will judged to be intolerable.
Otherwise, the Expansion Cohort 2.1 dose will be the MTD for the study.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety. Systemic and locoregional Adverse Events (AEs) will be graded by CTCAE v4.0 and coded according to MedDRA. AE data for all subjects in the 1st cohort will be assessed prior to dose escalation. Final assessment use AE data for all subjects.
28 days
Yes
Eric Wachter, Ph.D.
Study Director
Provectus Pharmaceuticals
United States: Food and Drug Administration
PV-10-LC-01
NCT00986661
October 2009
December 2013
Name | Location |
---|---|
Sharp Memorial Hospital | San Diego, California 92123 |
The Southeastern Center for Digestive Disorders & Pancreatic Cancer | Tampa, Florida 33613 |