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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Cancer Metastatic to the Liver, Recurrent Hepatocellular Carcinoma

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Trial Information

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.


Inclusion Criteria:



- Age 18 years or older, males and females.

- Histologically or cytologically confirmed, or clinically diagnosed based on currently
accepted standards, cancer metastatic to the liver or HCC that is not amenable at the
time of enrollment to resection, transplant or other potentially curative therapy.

- The Target Lesion must be determined to be amenable to percutaneous injection by the
treating physician.

- The Target Lesion must have measurable disease, defined as a unidimensionally
measurable lesion ≥ 1.0 cm in longest diameter by helical CT.

- Performance status of Karnofsky scale 60%-100% or ECOG performance scale 0-2.

- Life expectancy ≥ 12 weeks.

- Hematopoietic Function: WBC ≥ 2,500/mm3; ANC ≥ 1000/mm3; Hemoglobin ≥ 8 g/dL;
Platelet count ≥ 50,000/mm3; Coagulation: INR ≤ 1.3.

- AST and ALT < 5 times ULN; ALP < 5 times ULN; Bilirubin ≤ 1.5 times ULN; Creatinine ≤
1.5 times ULN and eGFR ≥ 50.

- Thyroid Function: Total T3 or free T3, total T4 or free T4 and THS ≤ CTCAE Grade 2
abnormality.

- Renal Function: Adequate renal function in the opinion of the Investigator with no
clinically significant renal impairment or uncontrolled renal disease.

- Cardiovascular Function: Adequate cardiovascular function in the opinion of the
Investigator with no clinically significant uncontrolled cardiovascular disease.

- Respiratory Function: Adequate respiratory function in the opinion of the
Investigator with no clinically significant uncontrolled respiratory disease.

- Immunological Function: Adequate immune system function in the opinion of the
Investigator with no known immunodeficiency disease.

- Informed Consent: Signed by the subject prior to screening.

Exclusion Criteria:

- Primary HCC amenable to resection, transplant or other potentially curative therapy.

- Surgery: Subjects who have received hepatic surgery, ablation or chemoembolization
within 4 weeks of PV-10 administration.

- Radiation Therapy: Hepatic radiation within 4 weeks of PV-10 administration.

- Chemotherapy: Chemotherapy within 4 weeks of PV-10 administration (6 weeks for
nitrosoureas or mitomycin C). Subjects with HCC who have been on a stable dose of
sorafenib for at least 4 weeks will be candidates for enrollment in Expansion Cohort
2.

- Investigational Agents: Investigational agents within 4 weeks (or 5 half-lives) of
PV-10 administration.

- Phototoxic or Photosensitizing Agents: Concomitant agents posing a clinically
significant risk of photosensitivity reaction within 5 half-lives of PV-10
administration.

- Concurrent or Intercurrent Illness: Impaired wound healing due to diabetes;
Significant concurrent or intercurrent illness, psychiatric disorders or alcohol or
chemical dependence that would compromise Subject safety or compliance or interfere
with interpretation of the study; Uncontrolled thyroid disease (subclinical or
ongoing), goiter, partial thyroidectomy, previous radioiodine or surgically treated
Graves' hyperthyroidism or cystic fibrosis; Presence of clinically significant acute
or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal,
pulmonary, immunological (with the exception of the presence of hepatitis B virus
(HBV), viral hepatitis, or cirrhosis), endocrine, or central nervous system
disorders; Current encephalopathy or current treatment for encephalopathy; A
documented variceal hemorrhage within 4 months of screening; History of human
immunodeficiency virus or acquired immune deficiency syndrome; The clinical presence
of ascites.

- Pregnancy: Female subjects who are pregnant, lactating or have positive serum β HCG
pregnancy test taken within 7 days of PV-10 administration; Fertile subjects who are
not using effective contraception (e.g., oral contraceptives, intrauterine devices,
double barrier methods such as condoms and diaphragms, abstinence or equivalent
measures).

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Eric Wachter, Ph.D.

Investigator Role:

Study Director

Investigator Affiliation:

Provectus Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

PV-10-LC-01

NCT ID:

NCT00986661

Start Date:

October 2009

Completion Date:

December 2013

Related Keywords:

  • Cancer Metastatic to the Liver
  • Recurrent Hepatocellular Carcinoma
  • Carcinoma
  • Liver Neoplasms
  • Neoplasms
  • Neoplasms, Second Primary
  • Carcinoma, Hepatocellular

Name

Location

Sharp Memorial HospitalSan Diego, California  92123
The Southeastern Center for Digestive Disorders & Pancreatic CancerTampa, Florida  33613