NeoplasmsPhase 1NCT00195260

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

A Phase 1 study testing bosutinib in people with Neoplasms, run by Pfizer at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: bosutinib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 151 participants
Where: 19 sitesUnited States
Study dates: Oct 2004to Nov 2007
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

Pfizer Investigational Site
Atlanta, Georgia, 30341
Pfizer Investigational Site
Baltimore, Maryland, 21287
Pfizer Investigational Site
Birmington, Alabama, 35233
Pfizer Investigational Site
Charlotte, North Carolina, 28203
Pfizer Investigational Site
Charlotte, North Carolina, 28211
Pfizer Investigational Site
Cleveland, Ohio, 44106-1736
Pfizer Investigational Site
Detroit, Michigan, 48202
Pfizer Investigational Site
Indianpolis, Indiana, 46202
Pfizer Investigational Site
Lansing, Michigan, 48910
Pfizer Investigational Site
Los Angeles, California, 90033
Pfizer Investigational Site
New York, New York, 10016
Pfizer Investigational Site
New York, New York, 10032
Pfizer Investigational Site
San Antonio, Texas, 78258
Pfizer Investigational Site
Scottsdale, Arizona, 85258
Pfizer Investigational Site
Seattle, Washington, 98104
Pfizer Investigational Site
Tampa, Florida, 33612
Pfizer Investigational Site
Tyler, Texas, 75702
Pfizer Investigational Site
UNC Chapel Hill, North Carolina, 27514
Pfizer Investigational Site
UNC Chapel Hill, North Carolina, 27759

Other trials in United States

About this study

Official title: Phase I Dose-Escalation Study Of Oral SKI-606 In Subjects With Advanced Malignant Solid Tumors

Conditions: Neoplasms
Being tested: bosutinib
Keywords: Solid tumors
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT00195260
Study group	Role	What they receive
Dose escalation	Experimental	Dose finding study of monotherapy bosutinib in patients with advanced solid tumors. Receives: Drug: bosutinib
Colorectal Cancer	Experimental	Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population. Receives: Drug: bosutinib
Pancreatic Cancer	Experimental	Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population. Receives: Drug: bosutinib
Non-Small Cell Lung Cancer (NSCLC)	Experimental	Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population. Receives: Drug: bosutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Part 1 Day 1 up to Day 28

Secondary outcomes (13)

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).
Measured: 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.
Measured: Baseline up to end of treatment (Week 95)
Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray
Number of participants with PCS ECG findings is reported on-therapy (OT) and at final visit (FV). Criteria for PCS ECG findings: heart rate (HR) =<45 beats/minute (bpm) and decrease (Dec) >15/>=120 bpm and decrease of >15 bpm; PR interval (Int) >=220 millisecond (msec), increase (Inc) >=20 msec, QRS Int >=120 msec, corrected QT (QTc) and QTc using fridericia formula(QTcF) Int >500 msec, increase >60 msec; no sinus rhythm; overall ECG abnormal. Participants with at least 1 measurement exceeding the criteria for PCS are reported.
Measured: Baseline up to end of treatment (Week 95)
Concomitant Medications Used for Management of Adverse Events (AEs)
Number of participants taking any non-study medications which were administered from Day 1 up to end of treatment (Week 95) as a management of an AE was to be reported.
Measured: Day 1 up to end of treatment (Week 95)
Change From Baseline in Karnofsky Performance Score
Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (complete healthy status). Higher score means higher ability to perform daily tasks.
Measured: Baseline up to end of treatment (Week 95)
Number of Participants With Change From Baseline in Physical Examination
Physical examinations included body weight, height and vital signs and only finding that exceeded the criterion for PCS was weight. Criteria for weight was: an increase or decrease of >=10% from baseline.
Measured: Baseline up to end of treatment (Week 95)
Number of Participants With Change From Baseline in Opthalmologic Examination
Ophthalmologic evaluation included visual acuity, funduscopic examination, and any clinically-significant abnormality.
Measured: Baseline up to end of treatment (Week 95)
Overall Survival (OS) in Part 2
Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from death case report forms (CRFs) or from follow-up contact data (where the participant current status was death).
Measured: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
Progression Free Survival (PFS) in Part 2
Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD, or from death CRFs).
Measured: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
Maximum Observed Plasma Concentration (Cmax)
Measured: 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
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measured: 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
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 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
Area Under the Concentration-Time Curve (AUC)
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Steady state concentration was achieved at Day 15.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2004Nov 2007

First posted19 Sep 2005 (estimated)
Study startOct 2004
Primary completionNov 2007
Study completionNov 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 151 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00195260
Sponsor's protocol ID: 3160A1-100
Other IDs: B1871012
Status last verified: Jan 2013
First submitted: 12 Sep 2005
Last updated: 11 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 24919837

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Dose-Escalation Study Of Oral SKI-606 In Subjects With Advanced Malignant Solid Tumors
ClinicalTrials.gov ID: NCT00195260
Acronym / sponsor ID: 3160A1-100
Conditions: Neoplasms
Keywords: Solid tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 151 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: Oct 2004
Primary completion: Nov 2007 (actual)
Study completion: Nov 2007 (actual)
First posted: 19 Sep 2005 (estimated)
Results: Posted 11 Feb 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Dose escalation	Experimental	Drug: bosutinibDose finding study of monotherapy bosutinib in patients with advanced solid tumors.
Colorectal Cancer	Experimental	Drug: bosutinibEnroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.
Pancreatic Cancer	Experimental	Drug: bosutinibEnroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.
Non-Small Cell Lung Cancer (NSCLC)	Experimental	Drug: bosutinibEnroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
bosutinibDose 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.	Drug	Dose escalation
bosutinib400mg QD bosutinib, as long as tolerated and disease under study does not worsen.	Drug	Colorectal Cancer
bosutinib400mg QD bosutinib, as long as tolerated and disease under study does not worsen.	Drug	Pancreatic Cancer
bosutinib400mg QD bosutinib, as long as tolerated and disease under study does not worsen.	Drug	Non-Small Cell Lung Cancer (NSCLC)

Primary outcome

Number of Participants With Dose-limiting Toxicities (DLT) in Part 1
Time frame: Part 1 Baseline up to Day 28
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.
Number of Participants With Adverse Events (AEs) by Seriousness
Time frame: Baseline up to 30 days after last dose
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.
Duration of Most Frequently Observed Adverse Events (AEs)
Time frame: Baseline up to 30 days after last dose
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.
Number of Participants With Best Overall Response (BOR) in Part 1
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
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.
Number of Participants With Best Overall Response (BOR) in Part 2
Time frame: 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
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.
Maximum Tolerated Dose (MTD) in Part 1
Time frame: Part 1 Day 1 up to Day 28
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.

13 secondary outcomes

Maximum Tolerated Dose (MTD) for Prolonged Use
Time frame: Part 1 Day 1 up to Day 28
Number of Participants With Change From Baseline in Laboratory Test Results
Time frame: Baseline up to end of treatment (Week 95)
Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray
Time frame: Baseline up to end of treatment (Week 95)
Concomitant Medications Used for Management of Adverse Events (AEs)
Time frame: Day 1 up to end of treatment (Week 95)
Change From Baseline in Karnofsky Performance Score
Time frame: Baseline up to end of treatment (Week 95)
Number of Participants With Change From Baseline in Physical Examination
Time frame: Baseline up to end of treatment (Week 95)
Number of Participants With Change From Baseline in Opthalmologic Examination
Time frame: Baseline up to end of treatment (Week 95)
Overall Survival (OS) in Part 2
Time frame: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
Progression Free Survival (PFS) in Part 2
Time frame: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
Maximum Observed Plasma Concentration (Cmax)
Time frame: 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
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 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
Plasma Decay Half-Life (t1/2)
Time frame: 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
Area Under the Concentration-Time Curve (AUC)
Time frame: 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

Results and safety

Results posted to the registry on 11 Feb 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bosutinib 50 mg	4	0
Bosutinib 100 mg	4	0
Bosutinib 200 mg	6	0
Bosutinib 300 mg	7	0
Bosutinib 400 mg	7	0
Bosutinib 500 mg	7	0
Bosutinib 600 mg	10	0
Maximum Tolerated Dose (MTD) lead-in	6	0
Colorectal Cancer	0	0
Pancreatic Cancer	0	0
Non-small Cell Lung Cancer (NSCLC)	0	0

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

Time frame: Part 1 Baseline up to Day 28. Number. Unit: participants

Measure	Bosutinib 50 mg n = 4	Bosutinib 100 mg n = 4	Bosutinib 200 mg n = 6	Bosutinib 300 mg n = 7	Bosutinib 400 mg n = 7	Bosutinib 500 mg n = 7	Bosutinib 600 mg n = 10	MTD-lead in n = 6
Value	0	0	1	1	0	1	3	0

Population analysed: Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.

Primary outcome: Number of Participants With Adverse Events (AEs) by Seriousness

Time frame: Baseline up to 30 days after last dose. Number. Unit: participants

Measure	Bosutinib 50 mg n = 4	Bosutinib 100 mg n = 4	Bosutinib 200 mg n = 6	Bosutinib 300 mg n = 7	Bosutinib 400 mg n = 7	Bosutinib 500 mg n = 7	Bosutinib 600 mg n = 10	MTD-lead in n = 6	RP2D 400 mg n = 100
AEs	4	4	6	7	7	7	10	6	100
Serious adverse events (SAEs)	4	3	2	3	5	2	7	3	47

Population analysed: Safety population included all participants who had taken at least 1 dose of study medication.

Primary outcome: Duration of Most Frequently Observed Adverse Events (AEs)

Time frame: Baseline up to 30 days after last dose. Median (Full Range). Unit: days

Measure	Bosutinib 50 mg n = 4	Bosutinib 100 mg n = 4	Bosutinib 200 mg n = 6	Bosutinib 300 mg n = 7	Bosutinib 400 mg n = 7	Bosutinib 500 mg n = 7	Bosutinib 600 mg n = 10	MTD lead-in n = 6	RP2D 400 mg n = 100
Diarrhea	1.0 (1 to 1)	NA (NA to NA)	12.0 (1 to 27)	2.0 (1 to 15)	3.5 (1 to 7)	7.0 (1 to 33)	1.0 (1 to 23)	1.0 (1 to 30)	3.0 (1 to 75)
Nausea	2.0 (1 to 14)	1.0 (1 to 11)	1.0 (1 to 8)	9.0 (1 to 366)	4.0 (1 to 15)	7.0 (1 to 94)	3.0 (1 to 24)	7.0 (1 to 24)	13.0 (1 to 126)
Vomiting	2.5 (1 to 4)	1.0 (1 to 9)	NA (NA to NA)	1.0 (1 to 13)	3.0 (1 to 5)	1.0 (1 to 3)	2.0 (1 to 24)	2.5 (1 to 9)	2.0 (1 to 62)

Population analysed: Safety population included all participants who had taken at least 1 dose of study medication.

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

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. Number. Unit: participants

Measure	Bosutinib 50 mg n = 3	Bosutinib 100 mg n = 3	Bosutinib 200 mg n = 6	Bosutinib 300 mg n = 6	Bosutinib 400 mg n = 6	Bosutinib 500 mg n = 6	Bosutinib 600 mg n = 4	MTD-lead in n = 3
Complete response	0	0	0	0	0	0	0	0
Partial response	0	0	0	0	0	1	0	0
Stable disease	0	2	2	5	3	2	4	2
Progressive disease	3	1	4	1	2	3	0	1
Indeterminate	0	0	0	0	1	0	0	0
Not done	0	0	0	0	0	0	0	0

Population analysed: Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.

13 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bosutinib 50 mg	4 of 4 (100%)	4 of 4 (100%)	Not reported
Bosutinib 100 mg	3 of 4 (75%)	4 of 4 (100%)	Not reported
Bosutinib 200 mg	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
Bosutinib 300 mg	3 of 7 (42.9%)	7 of 7 (100%)	Not reported
Bosutinib 400 mg	5 of 7 (71.4%)	7 of 7 (100%)	Not reported
Bosutinib 500 mg	2 of 7 (28.6%)	7 of 7 (100%)	Not reported
Bosutinib 600 mg	7 of 10 (70%)	10 of 10 (100%)	Not reported
MTD lead-in	3 of 6 (50%)	6 of 6 (100%)	Not reported
RP2D 400 mg	47 of 100 (47%)	99 of 100 (99%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24919837Hsyu 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bosutinib in people with Neoplasms, run by Pfizer at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 (time frame: Part 1 Baseline up to Day 28). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00195260, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2013.