PV-10 For Cancers of the Liver
PV-10 is an investigational new drug containing a proprietary injectable formulation of rose bengal disodium, a water-soluble xanthene dye currently in use in a topical opthalmic diagnostic. PV-10 is designed for injection into solid tumors (intralesional administration). Its oncology focus is on melanoma, breast cancer and cancers of the liver. Provectus has received orphan drug designations from the FDA for its melanoma and hepatocellular carcinoma indications.
- An Expanded Phase 1 trial, currently in progress, is expected to be completed in 2015.
- Over 270 cancer patients have been treated with PV-10, including 12 in a Phase 1 recurrent breast cancer study, 6 in a Phase 1 metastatic liver cancer study, 20 in a Phase 1 melanoma study, 80 in a Phase 2 melanoma study, 10 in an investigator-initiated study of PV-10 chemoablation followed by radiotherapy, and over 140 patients enrolled in the Compassionate Use Program for PV-10. Additionally, 11 of the 80 Phase 2 melanoma study subjects continued with the Compassionate Use Program.
Phase 1 Clinical Trial
- In July 2015, data from this phase 1 study of PV-10 for chemoablation of hepatocellular carcinoma (HCC) and cancer metastatic to the liver was presented at the 6th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2015) in Osaka, Japan in a poster presentation entitled "Phase 1 Study of PV-10 for Chemoablation of Hepatocellular Cancer and Cancer Metastatic to the Liver."
Based on the data presented, the researchers concluded that preliminary efficacy in treatment of liver tumors with PV-10, a 10% solution of rose Bengal, was observed with acceptable tolerability. The study is continuing at three study centers with two expansion cohorts to further assess safety and response in HCC and other cancers metastatic to the liver.
- In July 2015, data from this phase 1 study of PV-10 for chemoablation of hepatocellular carcinoma (HCC) and cancer metastatic to the liver was presented as a poster presentation at the ESMO 17th World Congress on Gastrointestinal Cancer (ESMO-GI). The main conclusion was that preliminary evidence of efficacy in treatment of liver cancers with PV-10 was observed.
- In September 2012, The study protocol was expanded to include the assessment of safety and efficacy in up to 24 additional patients with hepatocellular carcinoma or metastatic cancer of the liver (Expansion Cohort 1), as well as the safety and efficacy in up to 12 patients with HCC who are on a stable dose of sorafenib, a standard treatment for HCC (Expansion Cohort 2). In both expansion cohorts, subjects will receive PV-10 treatment of a single hepatic tumor. Subjects with multiple injectable tumors will be eligible for re-enrollment for treatment of additional tumors if PV-10 is well-tolerated. The initial Phase 1 study had included two cohorts, each consisting of three subjects; dose escalation for the second cohort occurred following assessment of safety and tolerability in the first cohort.
Efficacy assessment will be based on a two-dimensional European Association for the Study of the Liver (2D EASL) criteria, which has been shown to correlate with clinical outcome in studies of other ablative therapies. Follow-up for the protocol is also extended from 28 days to three months to allow for assessment of response to PV-10
- In April 2011, PV-10 received Orphan Drug Designation from the US FDA for the treatment of liver cancer.
- In January 2011, patient accrual and treatment of all six subjects was completed. Preliminary results show the treatment was generally well-tolerated, with substantial evidence of efficacy.
- In September 2010, enrollment was completed for the first dose cohort of three subjects. The therapy was very well tolerated by all three subjects treated, with substantial evidence of efficacy.
- In July 2010, it was reported that encouraging results were seen in two subjects following treatment of inoperable hepatocellular carcinoma tumors.
- In October 2009, subject enrollment began at Sharp Memorial Hospital in San Diego. The principal investigator at this clinical site is Paul Goldfarb, M.D.
- A Phase 1 study was initiated in October 2009 to evaluate the safety, tolerability, pharmacokinetics and effect on tumor growth following a single intralesional injection of PV-10 in subjects with either recurrent hepatocellular carcinoma (HCC) or cancer metastatic to the liver. In each of two planned dose cohorts there will be three subjects. Dose escalation will occur following assessment of safety and tolerability in the first cohort.
Primary Outcome Measures:
- Safety. Systemic and locoregional Adverse Events (AEs) will be graded by CTCAE v3.0 and coded according to MedDRA. AE data for all subjects in the first cohort will be assessed prior to dose escalation. Final assessment use AE data for all subjects. [ Time Frame: 28 days ]
Secondary Outcome Measures
- Lesion distribution and retention of PV-10 following injection. [ Time Frame: 28 days ]
- Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by modified RECIST. [ Time Frame: 28 days ]
- Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin and GGT. [ Time Frame: 28 days ]
- Pharmacokinetics of PV-10 in the bloodstream following intralesional injection. Samples will be obtained immediately prior to PV-10 injection and at 2, 4, 8, 24 and 72 hours, and 7, 14 and 28 days to assess uptake and excretion of PV-10. [ Time Frame: 28 days ]