Title
PR-104 in Treating Patients With Advanced Solid Tumors
A Phase I, Multi-Center, Open Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR-104 Given Every 3 Weeks in Patients With Solid Tumors
Phase
Phase 1Lead Sponsor
Proacta, IncorporatedStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Unspecified Adult Solid Tumor, Protocol SpecificIntervention/Treatment
pr-104 ...Study Participants
27RATIONALE: 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.
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.
PR104 was administered as a 1-hr IV infusion every 21 days at doses ranging from 135 to 1400 mg/m2
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)
