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Randomized Phase 1/2 Open-Label Trial of PR104 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

NCT00862082 · Status: TERMINATED · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 14

Last updated 2013-08-23

Study results available
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Summary

The current understanding of PR104 justifies the evaluation of PR104 with sorafenib in patients with hepatocellular carcinoma. These include:

* Hypoxia. Hepatocellular Carcinoma (HCC) is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M. In addition, in preclinical models, sorafenib has been demonstrated to increase the degree of hypoxia in tumors following treatment.
* Non-overlapping toxicity. PR104 and sorafenib do not share major toxicities. It is anticipated that both drugs can be administered at their full single agent dose when used in combination.
* Aldo-keto reductase 1C3 (AKR1C3). HCC has been shown to express high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic HCC cells.
* Preclinical data. The use of sorafenib and PR104 alone and in combination in a hepatocellular carcinoma model demonstrates activity of PR104 as a single agent and increased activity when PR104 and sorafenib are used in combination.

The current study will provide an estimate of the activity of PR104 in subjects with HCC. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity in HCC to warrant a larger phase III registration study in this indication.

Primary objectives

* Phase I: Determine the maximum tolerated dose (MTD) of PR104 when used in combination with standard dose sorafenib
* Phase II: Estimate the response rate (RR) of PR104/sorafenib \[Note: Phase II was never initiated\]

Secondary objectives

* Evaluate survival
* Evaluate Progression Free Survival (PFS)
* Evaluate time to progression (TTP)
* Evaluate safety
* Evaluate the pharmacokinetics (PK) of sorafenib, PR104 and PR104 metabolites
* Collect diagnostic biopsy samples for the determination of aldo-keto reductase 1C3
* Collect plasma samples for assessment of potential biomarkers of tumor hypoxia

Conditions

Interventions

DRUG

PR104 550 mg/m^2 + sorafenib

550 mg/m\^2 PR104 IV on day 1 of each 28 day cycle + 400 mg sorafenib PO twice daily. Number of Cycles: until progression or unacceptable toxicity develops.

DRUG

PR104 770 mg/m^2 + sorafenib

770 mg/m\^2 PR104 IV on day 1 of each 28 day cycle + 400 mg sorafenib PO twice daily. Number of Cycles: until progression or unacceptable toxicity develops.

Sponsors & Collaborators

  • Proacta, Incorporated

    lead INDUSTRY

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2009-03-31
Primary Completion
2010-01-31
Completion
2010-05-31

Countries

  • United States
  • Hong Kong
  • Singapore
  • Taiwan

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00862082 on ClinicalTrials.gov