PR-104 and Docetaxel or Gemcitabine in Treating Patients With Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as PR-104, docetaxel, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 when given together with docetaxel or gemcitabine in treating patients with solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Maximum tolerated dose of PR-104 [ Designated as safety issue: Yes ]
- Safety of PR-104 as measured by CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
- Dose-limiting toxicity of PR-104 [ Designated as safety issue: Yes ]
- Pharmacokinetics of PR-104 and its alcohol metabolite in the blood [ Designated as safety issue: No ]
- Pharmacokinetics of gemcitabine and docetaxel in the presence of PR-104 [ Designated as safety issue: No ]
- Antitumor activity [ Designated as safety issue: No ]
|Study Start Date:||February 2007|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
- 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 these patients.
- 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 day 1.
- 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.
|United States, California|
|San Diego, California, United States, 92121|
|University of Auckland Cancer Center|
|Auckland, New Zealand|
|Hamilton, New Zealand, 2020|
|Study Chair:||Terri J. Melink, NP, MSN, ANP||Proacta, Incorporated|