Clinical trial NCT01014429: Study of NMS-1286937 in Adult Patients With Advanced/Metastatic Solid Tumors
Official title: A Phase I Dose Escalation Study of NMS-1286937 Administered to Adult Patients With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Keywords: Phase I dose escalation study
Advanced or metastatic solid tumors
PLK 1 inhibitor
Adult patients
Lead sponsor: Nerviano Medical Sciences
Sponsor class: INDUSTRY
First posted: 2009-11-17
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) and first cycle dose limiting toxicities (DLTs)
timeFrame: Cycle 1
Secondary outcomes:
measure: 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)
timeFrame: Cycles 1 and 2
measure: Evaluation of pharmacodynamics: biomarkers modulation in skin and/or tumor samples of consenting patients
timeFrame: Cycles 1 and 2
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Arizona TGen Clinical Research Services at Scottsdale Heathcare
state: Arizona
Study officials:
affiliation: Nerviano Medical Sciences
name: Mariangela Mariani, Biol Sci D
role: STUDY_DIRECTOR
affiliation: Nerviano Medical Sciences
name: Maria Adele Pacciarini, Biol Sci D
role: STUDY_DIRECTOR
affiliation: Arizona TGen Clinical Reserch Services at Scottsdale Healthcare
name: Glen J Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References: