Study Evaluating SKI-606 (Bosutinib) In Advanced Malignant Solid Tumors

Phase 1CompletedNCT00195260

Pfizer151 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

151

Conditions

Neoplasms

Interventions

bosutinibDRUG

Dose levels evaluated 50mg, 100mg, 200mg, 300mg, 400mg, 500mg and 600mg. 500mg was identified as MTD, however due to GI toxicities at that dose, 400mg was selected as the RP2D. Drug was administered as long as tolerable and disease under study did not worsen.

bosutinibDRUG

400mg QD bosutinib, as long as tolerated and disease under study does not worsen.

bosutinibDRUG

400mg QD bosutinib, as long as tolerated and disease under study does not worsen.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (19)

Pfizer Investigational Site

Birmington, Alabama, United States

Pfizer Investigational Site

Scottsdale, Arizona, United States

Outcomes

Primary Outcomes

Number of Participants With Dose-limiting Toxicities (DLT) in Part 1

DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of greater than or equal to (\>=) 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to less than or equal to \[=\<\] grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.

Time frame: Part 1 Baseline up to Day 28

Number of Participants With Adverse Events (AEs) by Seriousness

Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category.

Time frame: Baseline up to 30 days after last dose

Duration of Most Frequently Observed Adverse Events (AEs)

The most frequently observed treatment-emergent AEs were gastrointestinal disorders which included diarrhea, nausea and vomiting. Duration of AE per event is calculated as AE stop date minus AE start date plus 1.

Time frame: Baseline up to 30 days after last dose

Number of Participants With Best Overall Response (BOR) in Part 1

BOR:investigator assessment by modified Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response:disappearance of all lesions. Partial Response (PR):\>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):\>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

Time frame: 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

Data from ClinicalTrials.gov

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Secondary Outcomes

Maximum Tolerated Dose (MTD) for Prolonged Use

MTD for prolonged use was the highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1) and was selected as recommended dose in Phase 2, due to substantial number of Grade 2 gastrointestinal toxicities observed in the MTD lead-in cohort (500 mg).

Time frame: Part 1 Day 1 up to Day 28

Number of Participants With Change From Baseline in Laboratory Test Results

Criteria for potentially clinically significant (PCS) laboratory values: albumin \<20, hemoglobin \<80 gram/liter(g/L); alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase \>5\*upper limit of normal(ULN) milliunit/milliliter(mU/mL); bilirubin total, creatinine\>3\*ULN micromole/L; calcium \<1.75 and \>3.1,potassium \<3 and \>6, sodium \<130, glucose \<2.2,phosphorous \<0.6 millimole/L; international normalized ratio \>2\*ULN, partial thromboplastin time, prothrombin time \>2\*ULN seconds; platelet count \<50\*10\^9/L. Participants meeting at least 1 PCS criteria are reported.