pr-104 in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

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.

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.

Eligibility 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)

Keywords: unspecified adult solid tumor, protocol specific