Clinical trial NCT00195260: Study Evaluating SKI-606 (Bosutinib) In Advanced Malignant Solid Tumors
Official title: Phase I Dose-Escalation Study Of Oral SKI-606 In Subjects With Advanced Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Solid tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-09-19
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of oral SKI-606 (bosutinib) administered on a daily schedule to subjects with advanced malignant solid tumors and to define a maximum tolerated dose (MTD) in this subject population.


Eligibility criteria: Inclusion Criteria:

* Advanced or recurrent solid malignancy confirmed histologically or cytologically for which no effective therapy is available.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
* Measurable disease as outlined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* Other inclusion applies.

Exclusion Criteria:

* Use of any systemic antitumor agents or any investigational agent within 28 days before the first dose of test article is administered.
* Prior exposure to SKI-606 or any other Src-kinase inhibitor, major surgery or radiotherapy within 14 days before the first dose of test article (recovery from previous surgery should be complete before day 1).
* Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth (Treated CNS metastases must be stable for \>= 2 weeks before day 1).
* Other exclusion applies.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLT) in Part 1
timeFrame: Part 1 Baseline up to Day 28
measure: Number of Participants With Adverse Events (AEs) by Seriousness
timeFrame: Baseline up to 30 days after last dose
measure: Duration of Most Frequently Observed Adverse Events (AEs)
timeFrame: Baseline up to 30 days after last dose
measure: Number of Participants With Best Overall Response (BOR) in Part 1
timeFrame: Part 1 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose
measure: Number of Participants With Best Overall Response (BOR) in Part 2
timeFrame: Part 2 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose
measure: Maximum Tolerated Dose (MTD) in Part 1
timeFrame: Part 1 Day 1 up to Day 28
Secondary outcomes:
measure: Maximum Tolerated Dose (MTD) for Prolonged Use
timeFrame: Part 1 Day 1 up to Day 28
measure: Number of Participants With Change From Baseline in Laboratory Test Results
timeFrame: Baseline up to end of treatment (Week 95)
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray
timeFrame: Baseline up to end of treatment (Week 95)
measure: Concomitant Medications Used for Management of Adverse Events (AEs)
timeFrame: Day 1 up to end of treatment (Week 95)
measure: Change From Baseline in Karnofsky Performance Score
timeFrame: Baseline up to end of treatment (Week 95)
measure: Number of Participants With Change From Baseline in Physical Examination
timeFrame: Baseline up to end of treatment (Week 95)
measure: Number of Participants With Change From Baseline in Opthalmologic Examination
timeFrame: Baseline up to end of treatment (Week 95)
measure: Overall Survival (OS) in Part 2
timeFrame: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
measure: Progression Free Survival (PFS) in Part 2
timeFrame: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
measure: Area Under the Concentration-Time Curve (AUC)
timeFrame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
Other outcomes:
measure: Gene Expression at Baseline
timeFrame: Baseline
Locations:
city: Birmington
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Scottsdale
country: United States
facility: Pfizer Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Tampa
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Indianpolis
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Lansing
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Charlotte
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: UNC Chapel Hill
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: UNC Chapel Hill
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: San Antonio
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Tyler
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Hsyu PH, Mould DR, Abbas R, Amantea M. Population pharmacokinetic and pharmacodynamic analysis of bosutinib. Drug Metab Pharmacokinet. 2014;29(6):441-8. doi: 10.2133/dmpk.DMPK-13-RG-126. Epub 2014 Jun 10.