Liver Clinical Trials
A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of PV-10 Chemoablation of Cancer Metastatic to the Liver or Hepatocellular Carcinoma not Amenable to Resection or Transplant
Treatment Agent: PV-10
Synopsis: The purpose of this study is to find out If PV-10 can be safely injected into liver tumors. The study also wants to know If PV-10 given directly into your tumor will have any effect on nearby tumor. Lastly the study wants to know if treatment with PV-10 is effective against your type of liver cancer, and if PV-10 can be given safely to people taking the anticancer drug sorafenib. PV-10 is being studied for the treatment of primary liver cancer (also called hepatocellular cancer or hepatoma) and other types of cancer that have spread to the liver (liver metastases).
PV-10 consists of a red dye called rose bengal that is dissolved in a sterile salt solution. Rose bengal has been approved for use in the United States as an intravenous (into a vein) injection to diagnose certain kinds of liver disease. Eye drops and paper strips containing rose bengal have also been approved in the U.S. and Europe for diagnosing eye disorders.
PV-10 is an investigational drug. This means that it has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of liver cancer, liver metastases or other types of cancer, and is still in the testing (experimental) stage. PV-10 has been tested in approximately 200 people with melanoma skin cancer and breast cancer to date. This research study is the first in which PV-10 will be tested for treatment of liver cancer.
PV-10 is a drug that is taken up mainly into cancer cells while being quickly cleared from normal cells around the cancerous tumor. This may allow PV-10 to kill the cancer cells while sparing healthy tissue around the tumor. In order to keep as much PV-10 as possible in the tumor, it will be injected directly into the tumor, where it is thought to remain for a period of time.
- 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; the maximum diameter of the Target Lesion shall be ≤ 4.9 cm.
- 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="" ≥="" />
- 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.
- Target Lesion(s) must not be contiguous with, encompass or infiltrate major blood vessels.
- 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 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).