Safety Study of PRLX 93936 in Patients With Advanced Solid Tumors

Prolexys Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Cancer

Treatments

Drug: PRLX 93936

Study type

Interventional

Funder types

Industry

Identifiers

NCT00528047

PRLX93936-0001

Details and patient eligibility

About

The purpose of this study is to test the safety of PRLX 93936 and see what kind of effect it has on patients and their cancer. This study will also determine the highest dose of PRLX 93936 that can be given without causing adverse side effects and the dose of PRLX 93936 that should be used in future studies.

Full description

This study will assess the safety, pharmacokinetics, and pharmacodynamics of PRLX 93936 administered intravenously over 1 hr daily for 5 days in patients with advanced solid tumors. Patients will be evaluated prior to dosing, during dosing and following dosing, on a 28-day cycle. Tumor response will be evaluated every other cycle.

Three patients will be assigned per dose level until the Maximum Tolerated Dose (MTD) is reached or a a Dose-Limited Toxicity (DLT) is encountered. Sequential cohorts of three patients will be treated with escalating doses until the Maximum Tolerated Dose (MTD) is reached.

Enrollment

37 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed solid tumors
Tumor progression after receiving standard/approved chemotherapy and for whom no available treatment provides clinical benefit
One or more metastatic tumors measurable on a CT scan or MRI per RECIST criteria
ECOG performance 0-1
Life expectancy of at least 3 months
Age >/= 18 years
A negative pregnancy test (if female of child-bearing potential)
Acceptable liver function:
Bilirubin </= 1.5 times the Upper Limit of Normal (ULN)
AST (SGOT), ALT (SGPT) and Alkaline phosphatase </= 2.5 times ULN (if liver metastases are present, then </= 5 times ULN is allowed)
Acceptable renal function:
Serum creatinine within normal limits, OR calculated creatinine clearance >/= 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal
Acceptable hematologic status:
Granulocyte count >/= 1500 cells/mm3
Platelet count >/= 100,000 (plt/mm3)
Hemoglobin >/= 9.0 g/dL
Urinalysis: no clinically significant abnormalities
Acceptable coagulation status:
PT within normal limits
aPTT within normal limits
Completed any chemotherapy, major surgery, or irradiation at least four weeks before enrollment in this study (six weeks for mitomycin-C or nitrosoureas, and two weeks for "targeted" therapies such as kinase inhibitors). Patient must have recovered from all toxicities incurred as a result of previous therapy.
QT intervals of QTC </= 450 msec for men and </= 470 msec for women (as measured by Hodges equation)
Left ventricular ejection fraction >/= 50% by 2D Echocardiogram (or > institutional lower limits of normal)

Exclusion criteria

NYHA Class III or IV, cardiac disease, myocardial infarction within the past six months, unstable arrhythmia, or evidence of ischemia on ECG
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Pregnant or nursing women
Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within four weeks prior to study entry (six weeks for mitomycin-C or nitrosoureas and two weeks for targeted therapies such as kinase inhibitors).
Unwillingness or inability to comply with protocol procedures
Known current infection with HIV, hepatitis B or hepatitis C
Currently receiving any other investigational agent
Currently receiving medications metabolized by the cytochrome P450 3A4 enzyme pathway
Presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with brain metastases which are well controlled (patients not taking dexamethasone or anti-seizure medication >/= three months after treatment) may be enrolled.
Any other severe concurrent disease, which in the judgement of the investigator would make the patient inappropriate for the study
Diagnosis of hypertension
Previously enrolled in this trial