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
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of PR-104 in combination with docetaxel or
gemcitabine hydrochloride in patients with solid tumors.
Secondary
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor malignancy
- Treatment with either docetaxel or gemcitabine hydrochloride in combination with an
investigational agent is reasonable
- Measurable or evaluable disease
PATIENT CHARACTERISTICS:
- ECOG performance status of 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9.0 g/dL (red blood cell transfusion allowed)
- Bilirubin normal
- ALT and AST ≤ 2.5 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN
- PT/INR or aPTT ≤ 1.1 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 30 days after
completion of study therapy
- No evidence of any other significant medical disorder, including uncontrolled
infection or infection requiring a concurrent parenteral antibiotic, or laboratory
finding that, in the opinion of the investigator, would preclude study compliance
- No known HIV positivity
- No hepatitis B surface antigen positivity
- No hepatitis C positivity with abnormal liver function test
PRIOR CONCURRENT THERAPY:
- No prior radiotherapy to > 25% of bone marrow
- No prior high-dose chemotherapy (including conditioning for either myeloablative or
nonmyeloablative transplantation)
- No more than 3 prior chemotherapy regimens
- More than 4 weeks since prior major surgery
- More than 4 weeks since prior investigational or traditional anticancer therapy
(including radiotherapy) (6 weeks for nitrosoureas and mitomycin C)
- The following medications/treatments are not permitted during the trial:
- Any other licensed or investigational anticancer treatment
- Prophylactic hematopoietic growth factors
- Irradiation therapy (palliative or therapeutic) unless given in the absence of
tumor progression
- Concurrent systemic steroids allowed provided the patient is on a stable dose for ≥ 2
weeks prior to study treatment
- Concurrent androgen-deprivation therapy allowed
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of PR-104
Safety Issue:
Yes
Principal Investigator
Terri J. Melink, NP, MSN, ANP
Investigator Role:
Study Chair
Investigator Affiliation:
Proacta, Incorporated
Authority:
United States: Food and Drug Administration
Study ID:
PR104-1003
NCT ID:
NCT00459836
Start Date:
February 2007
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Proacta, Incorporated | San Diego, California 92121 |
