A Study to Assess PV-10 Chemoablation of Cancer of the Liver
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|ClinicalTrials.gov Identifier: NCT00986661|
Recruitment Status : Recruiting
First Posted : September 30, 2009
Last Update Posted : April 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cancer Metastatic to the Liver Hepatocellular Carcinoma||Drug: PV-10 (10% rose bengal disodium)||Phase 1|
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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 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 48 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.
Subjects in Expansion Cohort 1 or Expansion Cohort 2 with more than one injectable tumor ≥ 1 cm in diameter will be eligible for treatment of an additional injectable tumor 28 days to 120 days after prior PV-10 administration provided that any prior treatments with PV-10 were well tolerated. This may be repeated until all injectable tumors ≥ 1 cm in diameter have received PV-10.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 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|
|Study Start Date :||October 2009|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||February 2020|
Experimental: PV-10 Injection (Intralesional)
Subjects in each of three cohorts will receive a single dose of PV-10 to one Target Lesion.
Drug: PV-10 (10% rose bengal disodium)
Subjects will receive a single injection of PV-10 to a single Target Lesion (0.25 mL PV-10 per cc lesion volume, Lv, or 0.50 mL PV-10 per cc Lv).
- 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. [ Time Frame: 28 days ]
- Lesion distribution and retention of PV-10 following injection. [ Time Frame: 3 months ]
- Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL criteria. [ Time Frame: 3 months ]
- Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin and GGT. [ Time Frame: 3 months ]
- 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 ]
- Pharmacokinetics of sorafenib 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 impact of PV-10 on sorafenib levels. [ Time Frame: 28 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00986661
|Contact: Paul M Goldfarb, M.D.||858 637 firstname.lastname@example.org|
|Contact: Eric Wachter, Ph.D.||865-769-4011 ext email@example.com|
|United States, California|
|Sharp Memorial Hospital||Recruiting|
|San Diego, California, United States, 92123|
|Contact: Amy King 858-939-5052 Amy.King@sharp.com|
|Principal Investigator: Kristin Rice, M.D.|
|United States, Florida|
|Florida Hospital Tampa||Recruiting|
|Tampa, Florida, United States, 33613|
|Contact: Heather Bingaman, BS 813-615-7068 firstname.lastname@example.org|
|Principal Investigator: Alexander Rosemurgy, M.D.|
|United States, Pennsylvania|
|St Luke's University Health Network||Recruiting|
|Bethlehem, Pennsylvania, United States, 18015|
|Contact: Alyse M LaLiberte, MPH 484-503-4151 Alyse.LaLiberte@sluhn.org|
|Contact: Robyn Rex, RN, OCN, CCRP 484-503-4152 email@example.com|
|Principal Investigator: Sanjiv Agarwala, MD|
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Rhonda Combs, LPN 615-322-2260 firstname.lastname@example.org|
|Contact: Melissa Ford, MSN, PhD, RN 615-875-7143 email@example.com|
|Principal Investigator: Daniel Brown, MD|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Gener Balmes, RN, CCRP 713-794-4153 firstname.lastname@example.org|
|Principal Investigator: Sapna Patel, MD|
|Study Director:||Eric Wachter, Ph.D.||Provectus Biopharmaceuticals, Inc.|
|Principal Investigator:||Paul M Goldfarb, M.D.||Sharp Clinical Oncology Research|