Study Of Bosutinib With Capecitabine In Solid Tumors And Locally Advanced Or Metastatic Breast Cancer
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT00959946
Collaborator
(none)
32
7
1
17.9
4.6
0.3
Study Details
Study Description
Brief Summary
This is a research study in 2 parts assessing the following parameters of the combination of the study drug called bosutinib, and a drug called capecitabine: the safety, how well the subject's body handles the study drug, and preliminary anti-tumor activity as treatment for different types of cancers in part 1, and breast cancer only in part 2.
In part 1, subjects will receive bosutinib and capecitabine daily at different dose levels of each drug in order to determine the highest tolerated dose of the combination study treatment. In part 2, subjects will receive bosutinib and capecitabine at this highest tolerated dose to see how well the study treatment works to treat breast cancer. In addition, genetic research testing (research analyses involving genes and gene products) will be performed on biological samples from subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
The study was prematurely discontinued following Part 1 evaluation, when the sponsor concluded that further translational biomarker analyses were needed to better define the breast tumor biomarkers that predict sensitivity to Src family kinase inhibitors. Thus the Sponsor made a determination to stop the study after Part 1 as communicated to investigators on 02Dec2010 . No subjects were enrolled into Part 2 of this study. The study was not terminated due to safety reasons.
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Open-Label Study Of Bosutinib Administered In Combination With Capecitabine In Subjects With Solid Tumor And ErbB2 Negative Locally Advanced Or Metastatic Breast Cancer
Study Start Date
:
Sep 1, 2009
Actual Primary Completion Date
:
Mar 1, 2011
Actual Study Completion Date
:
Mar 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 In part 1 (phase 1), ascending and descending multiple oral doses of bosutinib + capecitabine. Doses in part 1 include capecitabine 750 mg/m2 BID on days 1-14 + bosutinib 200 mg QD; capecitabine 625 mg/m2 BID on days 1-14 + bosutinib 300 mg QD. Depending on safety, capecitabine can also be administered at 1000 mg/m2 BID and bosutinib can be administered at 200 mg/m2 QD. The MTD of the combination treatment determined from part 1, will be administered in part 2 (phase 2). |
Drug: Bosutinib
Doses in part 1 include bosutinib 200 mg QD; bosutinib 300 mg QD. Depending on safety bosutinib can be administered at 200 mg/m2 QD. The MTD of the combination treatment determined from part 1, will be administered in part 2 (phase 2).
Drug: Capecitabine
Doses in part 1 include capecitabine 750 mg/m2 BID on days 1-14; capecitabine 625 mg/m2 BID on days 1-14. Depending on safety, capecitabine can also be administered at 1000 mg/m2 BID. The MTD of the combination treatment determined from part 1, will be administered in part 2 (phase 2).
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) - Part 1 [Part 1 Baseline up to Day 21]
The MTD contour is defined as the dose combinations that achieve a toxicity rate (dose-limiting toxicity [DLT] rate) of less than (<) 1/3. The observed toxicity rates for all the reporting groups (to which at least 1 cohort of participants was allocated) was estimated by calculating the proportion of DLTs observed in the first 21 days of treatment at those reporting groups. DLT includes grade (Gr) 3/4 nausea, vomiting, diarrhea, or asthenia more than 3 days, Gr 4 hematologic toxicities, delayed study treatment administration due to dose toxicities by more than 3 weeks. Pre-defined criterion for MTD: if a higher dose level of capecitabine existed such that the same dose level of bosutinib had a DLT rate of <1/3, no MTD was recommended for that capecitabine dose and if even the lowest dose of bosutinib achieved a toxicity rate of greater than (>) 1/3, no MTD was recommended for that capecitabine dose level.
- Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Part 1 [Part 1 Baseline up to 28 days after last dose of study treatment]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
- Percentage of Participants With Objective Response - Part 2 [Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose]
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR is defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions (LDs) of the target lesions taking as a reference the baseline sum LDs.
Secondary Outcome Measures
- Best Overall Response - Part 1 [Part 1 Baseline, every 6 weeks up to 6 months]
Best overall response based on investigator's disease status assessment. CR: disappearance of all lesions. PR: at least 30% decrease in sum of LDs of target lesions taking as reference baseline sum LDs. Progressive disease (PD): at least 20% increase in sum of LD of target lesions taking as a reference smallest sum of the recorded LDs since treatment start, or the appearance of 1 or more new lesions. Stable disease (SD): neither sufficient shrinkage for PR nor sufficient increase for PD taking as reference smallest sum of LD since treatment started.
- Progression Free Survival (PFS) - Part 2 [Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose]
Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD), or from adverse event (AE) data (where the outcome was "Death").
- Clinical Benefit Rate - Part 2 [Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose]
Percent of participants with confirmed CR, PR or SD for at least 24 weeks on study according to RECIST. CR: disappearance of all lesions. PR: at least 30% decrease in sum of LDs of target lesions taking as reference baseline sum LDs. SD: neither sufficient shrinkage for PR nor sufficient increase for PD taking as reference smallest sum of LD since treatment started.
- Duration of Response (DR) - Part 2 [Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose]
Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
- Maximum Observed Plasma Concentration (Cmax) - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
- Apparent Volume of Distribution (Vz/F) - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
- Apparent Oral Clearance (CL/F) - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Terminal-Phase Disposition Rate Constant (λz) - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
The terminal-phase disposition rate constant measured by a log-linear regression of the terminal mono exponential portion of the observed plasma concentrations.
- Plasma Decay Half-Life (t1/2) - Part 2 [0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-life was to be calculated as 0.693/λz.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Part 1:
-
Ages eligible for study: 18 years or older.
-
Male and female.
-
Confirmed pathologic diagnosis of advanced breast cancer or pancreatic cancer or colorectal cancer or cholangiocarcinoma or glioblastoma not curable with available therapies, for whom bosutinib plus capecitabine is a reasonable treatment option.
Part 2:
-
Ages eligible for study: 18 years or older.
-
Female.
-
Confirmed pathologic diagnosis of locally advanced or metastatic breast cancer, or loco-regional recurrent breast cancer that is not amenable to curative treatment with surgery or radiotherapy.
-
Documented ER+ and/or PgR+/erbB2- or ER-/PgR-/erbB2- tumor based upon recently analyzed biopsy.
Exclusion Criteria:
Part 1:
-
Prior bosutinib, or any other prior Src inhibitor.
-
Prior chemotherapy with capecitabine or 5-FU for the treatment of metastatic disease is allowed unless patient stopped therapy for toxicity.
Part 2:
-
Prior bosutinib, or any other prior Src inhibitor prior chemotherapy with capecitabine or 5-FU for the treatment of metastatic disease.
-
Prior chemotherapy with capecitabine or 5-FU for adjuvant chemotherapy within the past 12 months.
-
erbB2+ breast cancer.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Boston | Massachusetts | United States | 02114 |
| 2 | Pfizer Investigational Site | Detroit | Michigan | United States | 84202 |
| 3 | Pfizer Investigational Site | Adelaide | South Australia | Australia | 5037 |
| 4 | Pfizer Investigational Site | Edegem | Belgium | 2650 | |
| 5 | Pfizer Investigational Site | Saint Herblain | France | 44805 | |
| 6 | Pfizer Investigational Site | Hong Kong | Hong Kong | ||
| 7 | Pfizer Investigational Site | Madrid | Spain | 28050 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00959946
Other Study ID Numbers:
- 3160A6-2208
- B1871011
First Posted:
Aug 17, 2009
Last Update Posted:
Feb 22, 2013
Last Verified:
Jan 1, 2013
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Study was pre-maturely terminated after part 1 (safety lead-in phase) of study and hence, planned treatments of part 2, Bosutinib 300 milligram (mg) + Capecitabine 1000 mg/square meter (mg/m^2) (Part 2): estrogen receptor positive (ER+) and Bosutinib 300 mg+Capecitabine 1000 mg/m^2 (Part 2): estrogen receptor negative (ER-), were not administered. |
| Arm/Group Title | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. |
| Period Title: Overall Study | ||||||||
| STARTED | 2 | 4 | 4 | 5 | 4 | 9 | 2 | 2 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 2 | 4 | 4 | 5 | 4 | 9 | 2 | 2 |
Baseline Characteristics
| Arm/Group Title | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Total of all reporting groups |
| Overall Participants | 2 | 4 | 4 | 5 | 4 | 9 | 2 | 2 | 32 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [Years] |
53.0
(4.24)
|
56.8
(16.32)
|
67.3
(10.05)
|
63.0
(8.43)
|
56.0
(8.45)
|
63.8
(5.49)
|
51.5
(6.36)
|
61.5
(4.95)
|
60.7
(9.24)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
2
100%
|
1
25%
|
2
50%
|
4
80%
|
3
75%
|
4
44.4%
|
1
50%
|
1
50%
|
18
56.3%
|
| Male |
0
0%
|
3
75%
|
2
50%
|
1
20%
|
1
25%
|
5
55.6%
|
1
50%
|
1
50%
|
14
43.8%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) - Part 1 |
|---|---|
| Description | The MTD contour is defined as the dose combinations that achieve a toxicity rate (dose-limiting toxicity [DLT] rate) of less than (<) 1/3. The observed toxicity rates for all the reporting groups (to which at least 1 cohort of participants was allocated) was estimated by calculating the proportion of DLTs observed in the first 21 days of treatment at those reporting groups. DLT includes grade (Gr) 3/4 nausea, vomiting, diarrhea, or asthenia more than 3 days, Gr 4 hematologic toxicities, delayed study treatment administration due to dose toxicities by more than 3 weeks. Pre-defined criterion for MTD: if a higher dose level of capecitabine existed such that the same dose level of bosutinib had a DLT rate of <1/3, no MTD was recommended for that capecitabine dose and if even the lowest dose of bosutinib achieved a toxicity rate of greater than (>) 1/3, no MTD was recommended for that capecitabine dose level. |
| Time Frame | Part 1 Baseline up to Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT evaluable population included all participants who received at least 14 doses of bosutinib and at least 10 doses of capecitabine in the first 21 days of treatment or had experienced a DLT within the first 21 days of treatment. N (number of participants analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Bosutinib + Capecitabine 625 mg/m^2 | Bosutinib + Capecitabine 750 mg/m^2 | Bosutinib + Capecitabine 1000 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Bosutinib 200 mg, or 300 mg, tablet administered orally once daily in a 21-day cycle. Capecitabine 625 mg/m^2 tablet administered orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg, 300 mg, or 400 mg tablet administered orally once daily in a 21-day cycle. Capecitabine 750 mg/m^2 tablet administered orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg, 300 mg, or 400 mg tablet administered orally once daily in a 21-day cycle. Capecitabine 1000 mg/m^2 tablet administered orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. |
| Measure Participants | 6 | 10 | 8 |
| Number [mg] |
NA
|
NA
|
300
|
| Title | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Part 1 |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Time Frame | Part 1 Baseline up to 28 days after last dose of study treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population: included participants who received at least 1 dose of the study medication. |
| Arm/Group Title | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. |
| Measure Participants | 2 | 4 | 4 | 5 | 4 | 9 | 2 | 2 |
| AEs |
100.0
5000%
|
100.0
2500%
|
100.0
2500%
|
100.0
2000%
|
100.0
2500%
|
100.0
1111.1%
|
100.0
5000%
|
100.0
5000%
|
| SAEs |
0.0
0%
|
50.0
1250%
|
50.0
1250%
|
40.0
800%
|
0.0
0%
|
33.3
370%
|
0.0
0%
|
50.0
2500%
|
| Title | Percentage of Participants With Objective Response - Part 2 |
|---|---|
| Description | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR is defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions (LDs) of the target lesions taking as a reference the baseline sum LDs. |
| Time Frame | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Best Overall Response - Part 1 |
|---|---|
| Description | Best overall response based on investigator's disease status assessment. CR: disappearance of all lesions. PR: at least 30% decrease in sum of LDs of target lesions taking as reference baseline sum LDs. Progressive disease (PD): at least 20% increase in sum of LD of target lesions taking as a reference smallest sum of the recorded LDs since treatment start, or the appearance of 1 or more new lesions. Stable disease (SD): neither sufficient shrinkage for PR nor sufficient increase for PD taking as reference smallest sum of LD since treatment started. |
| Time Frame | Part 1 Baseline, every 6 weeks up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol (PP) population included participants who received at least 14 doses of bosutinib and at least 10 doses of capecitabine within a 21-day period, had a baseline and at least 1 post-baseline tumor assessment, and had no major protocol violations. |
| Arm/Group Title | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. |
| Measure Participants | 1 | 4 | 4 | 5 | 4 | 9 | 2 | 1 |
| Complete Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Partial Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
50%
|
0
0%
|
0
0%
|
0
0%
|
| Stable Disease |
0
0%
|
1
25%
|
2
50%
|
0
0%
|
1
25%
|
6
66.7%
|
1
50%
|
1
50%
|
| Progressive Disease |
1
50%
|
3
75%
|
2
50%
|
5
100%
|
1
25%
|
2
22.2%
|
1
50%
|
0
0%
|
| Indeterminate |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
| Title | Progression Free Survival (PFS) - Part 2 |
|---|---|
| Description | Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD), or from adverse event (AE) data (where the outcome was "Death"). |
| Time Frame | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Clinical Benefit Rate - Part 2 |
|---|---|
| Description | Percent of participants with confirmed CR, PR or SD for at least 24 weeks on study according to RECIST. CR: disappearance of all lesions. PR: at least 30% decrease in sum of LDs of target lesions taking as reference baseline sum LDs. SD: neither sufficient shrinkage for PR nor sufficient increase for PD taking as reference smallest sum of LD since treatment started. |
| Time Frame | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Duration of Response (DR) - Part 2 |
|---|---|
| Description | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Time Frame | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Maximum Observed Plasma Concentration (Cmax) - Part 2 |
|---|---|
| Description | |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 2 |
|---|---|
| Description | |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Apparent Volume of Distribution (Vz/F) - Part 2 |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] - Part 2 |
|---|---|
| Description | AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Apparent Oral Clearance (CL/F) - Part 2 |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Terminal-Phase Disposition Rate Constant (λz) - Part 2 |
|---|---|
| Description | The terminal-phase disposition rate constant measured by a log-linear regression of the terminal mono exponential portion of the observed plasma concentrations. |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
| Title | Plasma Decay Half-Life (t1/2) - Part 2 |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-life was to be calculated as 0.693/λz. |
| Time Frame | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. |
| Arm/Group Title | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER+ | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 2): ER- |
|---|---|---|
| Arm/Group Description | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 negative (erbB2-). | Bosutinib 300 mg orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle, until disease progression, intolerable toxicity, or withdrawal of consent in participants with locally advanced or metastatic breast cancer having estrogen receptor negative (ER-) and/or progesterone receptor negative (PgR-) and human epidermal growth factor receptor 2 negative (erbB2-). |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||||||||||
| Arm/Group Title | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | ||||||||
| Arm/Group Description | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 200 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 625 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 300 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 750 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | Bosutinib 400 mg tablet orally once daily in a 21-day cycle along with capecitabine 1000 mg/m^2 tablet orally twice daily from Day 1 to 14, followed by 7 days off treatment in a 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. | ||||||||
All Cause Mortality |
||||||||||||||||
| Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | 2/4 (50%) | 2/4 (50%) | 2/5 (40%) | 0/4 (0%) | 3/9 (33.3%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Atrial fibrillation | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Gastrointestinal obstruction | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| General disorders | ||||||||||||||||
| Asthenia | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Chest pain | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Bronchitis | 0/2 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Glioblastoma multiforme | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Neoplasm malignant | 0/2 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Pancreatic carcinoma | 0/2 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Hemiparesis | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Renal impairment | 0/2 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Acute respiratory distress syndrome | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Dyspnoea | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | 4/4 (100%) | 3/4 (75%) | 5/5 (100%) | 4/4 (100%) | 9/9 (100%) | 2/2 (100%) | 2/2 (100%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Lymphopenia | 1/2 (50%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 1/2 (50%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 3/9 (33.3%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Abdominal pain upper | 1/2 (50%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 2/4 (50%) | 0/9 (0%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Constipation | 0/2 (0%) | 1/4 (25%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Diarrhoea | 2/2 (100%) | 1/4 (25%) | 2/4 (50%) | 3/5 (60%) | 3/4 (75%) | 8/9 (88.9%) | 2/2 (100%) | 2/2 (100%) | ||||||||
| Flatulence | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 1/4 (25%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Gastrooesophageal reflux disease | 1/2 (50%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 0/9 (0%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Nausea | 0/2 (0%) | 4/4 (100%) | 2/4 (50%) | 2/5 (40%) | 1/4 (25%) | 4/9 (44.4%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Vomiting | 0/2 (0%) | 3/4 (75%) | 1/4 (25%) | 0/5 (0%) | 1/4 (25%) | 2/9 (22.2%) | 2/2 (100%) | 0/2 (0%) | ||||||||
| General disorders | ||||||||||||||||
| Asthenia | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Fatigue | 0/2 (0%) | 2/4 (50%) | 1/4 (25%) | 3/5 (60%) | 1/4 (25%) | 5/9 (55.6%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Mucosal inflammation | 1/2 (50%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Oedema peripheral | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Pyrexia | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 1/4 (25%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Bronchitis | 0/2 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 1/4 (25%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Urinary tract infection | 1/2 (50%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Investigations | ||||||||||||||||
| Alanine aminotransferase increased | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 2/9 (22.2%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Aspartate aminotransferase increased | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Electrocardiogram QT prolonged | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 2/4 (50%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Weight decreased | 0/2 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 1/4 (25%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 0/2 (0%) | 2/4 (50%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 3/9 (33.3%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Hypophosphataemia | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 0/2 (0%) | 0/4 (0%) | 2/4 (50%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Back pain | 1/2 (50%) | 1/4 (25%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Musculoskeletal pain | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Pain in extremity | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 0/9 (0%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Dizziness | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 2/5 (40%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Headache | 0/2 (0%) | 1/4 (25%) | 0/4 (0%) | 0/5 (0%) | 1/4 (25%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Neuropathy peripheral | 0/2 (0%) | 1/4 (25%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Peripheral sensory neuropathy | 1/2 (50%) | 2/4 (50%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Psychiatric disorders | ||||||||||||||||
| Depression | 0/2 (0%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Insomnia | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 1/9 (11.1%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Urinary incontinence | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 1/2 (50%) | 0/4 (0%) | 1/4 (25%) | 1/5 (20%) | 0/4 (0%) | 2/9 (22.2%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Dyspnoea | 0/2 (0%) | 2/4 (50%) | 0/4 (0%) | 1/5 (20%) | 1/4 (25%) | 1/9 (11.1%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Dry skin | 1/2 (50%) | 0/4 (0%) | 1/4 (25%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | ||||||||
| Erythema | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 1/9 (11.1%) | 1/2 (50%) | 0/2 (0%) | ||||||||
| Palmar-plantar erythrodysaesthesia syndrome | 1/2 (50%) | 1/4 (25%) | 2/4 (50%) | 0/5 (0%) | 1/4 (25%) | 3/9 (33.3%) | 1/2 (50%) | 1/2 (50%) | ||||||||
| Pruritus | 1/2 (50%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/4 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | ||||||||
| Rash | 0/2 (0%) | 0/4 (0%) | 0/4 (0%) | 1/5 (20%) | 0/4 (0%) | 1/9 (11.1%) | 0/2 (0%) | 1/2 (50%) | ||||||||
Limitations/Caveats
Results are not provided because the study was terminated prior to part 2 due to unfavorable risk benefit ratio of the study treatment.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00959946
Other Study ID Numbers:
- 3160A6-2208
- B1871011
First Posted:
Aug 17, 2009
Last Update Posted:
Feb 22, 2013
Last Verified:
Jan 1, 2013