PR-104 in Treating Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as PR-104, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 in treating patients with advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
Primary
-
Evaluate the safety and tolerability of PR-104 in patients with advanced solid tumors.
-
Determine the maximum tolerated dose of PR-104 in these patients.
Secondary
-
Characterize the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.
-
Assess evidence of antitumor activity of this drug in these patients.
Tertiary
- Examine metabolic changes in tumors of these patients using fludeoxyglucose F 18 positron emission tomography scanning.
OUTLINE: This is a multicenter, open-label, prospective, uncontrolled, dose-escalation study.
Patients receive PR-104 IV over 60 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients 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 then periodically during study treatment for pharmacokinetic and tumor marker studies. Patients undergo fludeoxyglucose F 18 positron emission tomography scanning before beginning study treatment and after completion of course 2 to assess metabolic activity of the tumor.
After completion of study treatment, patients are followed at 30 days.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PR-104 PR104 was administered as a 1-hr IV infusion every 21 days at doses ranging from 135 to 1400 mg/m2 |
Drug: PR-104
Other: laboratory biomarker analysis
Other: pharmacological study
|
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically or cytologically confirmed solid tumor, meeting 1 of the following criteria:
-
Not amenable to standard therapy
-
Refractory to conventional therapy
-
Measurable or evaluable disease
PATIENT CHARACTERISTICS:
-
Karnofsky performance status 70-100%
-
Life expectancy > 3 months
-
Absolute neutrophil count ≥ 1,500/mm³
-
Platelet count ≥ 100,000/mm³
-
Hemoglobin > 9 g/L (transfusion independent)
-
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
-
ALT and AST ≤ 2.5 times ULN
-
Creatinine clearance ≥ 60 mL/min
-
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 treatment
-
No significant cardiac comorbidity including any of the following:
-
New York Heart Association class III-IV congenital heart failure
-
LVEF < 40%
-
Unstable angina
-
Myocardial infarction within the past 6 months
-
Ventricular arrhythmias requiring drug therapy
-
Pacemaker or implanted defibrillator
-
No ongoing coagulopathy
-
No uncontrolled infection or infection requiring parenteral antibiotics
-
No other significant clinical disorder or laboratory finding that would preclude study treatment
-
No known HIV positivity
-
No known positivity for hepatitis B surface antigen or hepatitis C with abnormal liver tests
-
No known allergy to nonplatinum-containing alkylating agents
PRIOR CONCURRENT THERAPY:
-
Recovered from prior therapy
-
More than 2 weeks since prior hormonal therapy (except for androgen-deprivation therapy)
-
More than 4 weeks since prior major surgery
-
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
-
More than 4 weeks since prior radiotherapy
-
More than 1 month since prior investigational drugs, therapies, or devices
-
No prior radiotherapy to > 25% of bone marrow
-
No prior high-dose chemotherapy, either myeloablative or nonmyeloablative (mini-allogeneic transplant)
-
No more than 3 prior myelosuppressive chemotherapy regimens
-
Concurrent steroids allowed provided dose is stable for ≥ 2 weeks and clinical condition is stable for 1 month
-
Nasal, opthalmologic, and topical glucocorticoid preparations allowed
-
Physiologic hormone replacement therapies allowed (i.e., oral replacement glucocorticoid therapy for adrenal insufficiency)
-
No concurrent prophylactic hematopoietic growth factors
-
No concurrent radiotherapy, including local palliative radiotherapy or systemic radioisotopes
-
Radioisotopes for protocol specified positron emission tomography allowed
-
No other concurrent investigational agents
-
No other concurrent chemotherapy, radiotherapy (including palliative local radiotherapy), hormonal therapy (except for androgen-deprivation therapy), and/or biological therapy (including immunotherapy)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jonsson Comprehensive Cancer Center at UCLA | Los Angeles | California | United States | 90095-1781 |
Sponsors and Collaborators
- Proacta, Incorporated
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Mark D. Pegram, MD, Jonsson Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PR104-1001
- P30CA016042
- UCLA-0512034-01A
- PROACTA-PR-104-1001