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

NCT00195260 | Completed Phase 1 Results

• 2 other identifiers: 3160A1-100B1871012
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 19

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.

Conditions

Neoplasms

Keywords

Solid tumors

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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

• Number of Participants With Best Overall Response (BOR) in Part 2

  BOR: investigator assessment by modified RECIST, recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. PR: \>=30% decrease in SLDs of TLs taking as reference baseline SLD. 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.

  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

• Maximum Tolerated Dose (MTD) in Part 1

  MTD: highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1). DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of \>= 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 =\< grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.

  Part 1 Day 1 up to Day 28

Secondary Outcomes (13)

• Maximum Tolerated Dose (MTD) for Prolonged Use

  Part 1 Day 1 up to Day 28

• Number of Participants With Change From Baseline in Laboratory Test Results

  Baseline up to end of treatment (Week 95)

• Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray

  Baseline up to end of treatment (Week 95)

• Concomitant Medications Used for Management of Adverse Events (AEs)

  Day 1 up to end of treatment (Week 95)

• Change From Baseline in Karnofsky Performance Score

  Baseline up to end of treatment (Week 95)

Other Outcomes (1)

• Gene Expression at Baseline

  Baseline

Study Arms (4)

Dose escalation

EXPERIMENTAL

Dose finding study of monotherapy bosutinib in patients with advanced solid tumors.

Drug: bosutinib

Colorectal Cancer

EXPERIMENTAL

Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Drug: bosutinib

Pancreatic Cancer

EXPERIMENTAL

Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Drug: bosutinib

Non-Small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Drug: bosutinib

Interventions

bosutinib DRUG

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.

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (19)

Pfizer Investigational Site

Birmington, Alabama, 35233, United States

Location

Pfizer Investigational Site

Scottsdale, Arizona, 85258, United States

Location

Pfizer Investigational Site

Los Angeles, California, 90033, United States

Location

Pfizer Investigational Site

Tampa, Florida, 33612, United States

Location

Pfizer Investigational Site

Atlanta, Georgia, 30341, United States

Location

Pfizer Investigational Site

Indianpolis, Indiana, 46202, United States

Location

Pfizer Investigational Site

Baltimore, Maryland, 21287, United States

Location

Pfizer Investigational Site

Detroit, Michigan, 48202, United States

Location

Pfizer Investigational Site

Lansing, Michigan, 48910, United States

Location

Pfizer Investigational Site

New York, New York, 10016, United States

Location

Pfizer Investigational Site

New York, New York, 10032, United States

Location

Pfizer Investigational Site

Charlotte, North Carolina, 28203, United States

Location

Pfizer Investigational Site

Charlotte, North Carolina, 28211, United States

Location

Pfizer Investigational Site

UNC Chapel Hill, North Carolina, 27514, United States

Location

Pfizer Investigational Site

UNC Chapel Hill, North Carolina, 27759, United States

Location

Pfizer Investigational Site

Cleveland, Ohio, 44106-1736, United States

Location

Pfizer Investigational Site

San Antonio, Texas, 78258, United States

Location

Pfizer Investigational Site

Tyler, Texas, 75702, United States

Location

Pfizer Investigational Site

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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.

  PMID: 24919837 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

bosutinib

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 19, 2005
• Study Start: October 1, 2004
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: February 11, 2013
• Results First Posted: February 11, 2013

Record last verified: 2013-01

Locations

US (19)