Advanced or Metastatic Solid Tumors
Conditions
Keywords
Phase I dose escalation study, Advanced or metastatic solid tumors, PLK 1 inhibitor, Adult patients
Brief summary
The purpose of this study is to evaluate the safety and tolerability of NMS-1286937, a polo-like-kinase 1 inhibitor, in patients with advanced metastatic solid tumor.
Interventions
DRUGNMS-1286937
Single Arm, dose escalation study. No. of cycles: until progression or unacceptable toxicity develops.
Sponsors
Nerviano Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced/metastatic solid tumors, for which no effective standard therapy exist * Adult patients (age \>/= 18) * ECOG performance status (PS) 0 or 1 * Life expectancy of at least 3 months * Adequate renal, liver function and bone marrow reserve * Prior cancer therapy allowed, with max 4 regimens of chemotherapy. Washout: at least 4 wks (6 wks for nitrosoureas, mitomycin C and liposomal doxorubicin) and all toxicities recovered to CTC Grade \</=1 * Prior radiotherapy allowed if no more than 25% of BM reserve irradiated * Women and men of child producing potential should agree to use effective contraception * Capability to swallow capsules intact
Exclusion criteria
* Known uncontrolled/symptomatic brain metastases * Currently active second malignancy * Major surgery in the last 4 wks * Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis * Pregnancy or breast-feeding women * Known active infections * History of drug allergic reactions * Gastrointestinal disease or other malabsorption syndromes that would impact on drug absorption. * Documented gastrointestinal ulcer * Other severe concurrent acute or chronic medical or psychiatric condition that could compromise protocol objectives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) and first cycle dose limiting toxicities (DLTs) | Cycle 1 |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of pharmacokinetics: plasma concentration at different times after dosing, area under the curve (AUC), maximum plasma concentration (Cmax), clearance (CL), volume of distribution, half-life (t½) | Cycles 1 and 2 |
| Evaluation of pharmacodynamics: biomarkers modulation in skin and/or tumor samples of consenting patients | Cycles 1 and 2 |
Countries
United States
Outcome results
None listed