A Phase Ib, Multi-Center, Open-Label, Dose Escalation Trial of Intravenous PR-104 Given in Combination With Docetaxel or Gemcitabine in Subjects With Solid Tumors
- Determine the maximum tolerated dose of PR-104 in combination with docetaxel or
gemcitabine hydrochloride in patients with solid tumors.
- Determine the safety of PR-104 in combination with docetaxel or gemcitabine
hydrochloride in these patients.
- Determine the antitumor activity of these regimens using disease-specific parameters,
such as exams, scans, and tumor markers, in these patients.
- Determine the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.
- Determine the pharmacokinetics of docetaxel and gemcitabine hydrochloride when
administered with PR-104.
- Collect plasma samples for assessment of potential biomarkers of tumor hypoxia from
- Examine metabolic changes in tumors using fludeoxyglucose F 18 positron emission
tomography (PET) and PET imaging with fluoromisonidazole F 18 (a hypoxia-targeted
radiopharmaceutical) in these patients.
OUTLINE: This is a nonrandomized, open-label, uncontrolled, multicenter, dose-escalation
study of PR-104. Patients are assigned to 1 of 2 treatment groups according to patient's
malignancy and prior treatment history.
- Group 1: Patients receive docetaxel IV over 60 minutes and PR-104 IV over 60 minutes on
- Group 2: Patients receive gemcitabine hydrochloride IV over 30 minutes and PR-104 IV
over 60 minutes on days 1 and 8.
In both groups, treatment repeats every 21 days for up to 8 courses in the absence of
unacceptable toxicity or disease progression.
Cohorts of 3-6 patients in each group receive escalating doses of PR-104 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
Blood is collected at baseline and periodically during course 1 for pharmacokinetic
analysis. Plasma samples are analyzed for biomarkers of tumor hypoxia at baseline and on
days 2 and 8.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of PR-104
Terri J. Melink, NP, MSN, ANP
United States: Food and Drug Administration
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