Study of NMS-1286937 in Adult Patients With Advanced/Metastatic Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Dose Escalation Study of NMS-1286937 Administered to Adult Patients With Advanced/Metastatic Solid Tumors

Conditions
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Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: NMS-1286937


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: NMS-1286937<br>* Single Arm, dose escalation study. No. of cycles: until progression or unacceptable toxicity develops.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) and first cycle dose limiting toxicities (DLTs) |  | Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I dose escalation study, Advanced or metastatic solid tumors, PLK 1 inhibitor, Adult patients