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| ID | Type | Description | Link |
|---|---|---|---|
| B1871011 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bosutinib | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) - Part 1 | 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. | Part 1 Baseline up to Day 21 |
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Part 1 | 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. | Part 1 Baseline up to 28 days after last dose of study treatment |
| Percentage of Participants With Objective Response - Part 2 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response - Part 1 | 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. |
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Inclusion Criteria:
Part 1:
Part 2:
Exclusion Criteria:
Part 1:
Part 2:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Boston | Massachusetts | 02114 | United States | ||
| Pfizer Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25290090 | Derived | Isakoff SJ, Wang D, Campone M, Calles A, Leip E, Turnbull K, Bardy-Bouxin N, Duvillie L, Calvo E. Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study. Br J Cancer. 2014 Nov 25;111(11):2058-66. doi: 10.1038/bjc.2014.508. Epub 2014 Oct 7. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Capecitabine | Drug | 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). |
|
| Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
| Part 1 Baseline, every 6 weeks up to 6 months |
| Progression Free Survival (PFS) - Part 2 | 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"). | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
| Clinical Benefit Rate - Part 2 | 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. | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
| Duration of Response (DR) - Part 2 | 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. | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
| 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 | 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. | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] - Part 2 | AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). | 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 Oral Clearance (CL/F) - Part 2 | 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. | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
| Terminal-Phase Disposition Rate Constant (λz) - Part 2 | The terminal-phase disposition rate constant measured by a log-linear regression of the terminal mono exponential portion of the observed plasma concentrations. | 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 (t1/2) - Part 2 | 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. | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
| Detroit |
| Michigan |
| 84202 |
| United States |
| Pfizer Investigational Site | Adelaide | South Australia | 5037 | Australia |
| Pfizer Investigational Site | Edegem | 2650 | Belgium |
| Pfizer Investigational Site | Saint-Herblain | 44805 | France |
| Pfizer Investigational Site | Hong Kong | Hong Kong |
| Pfizer Investigational Site | Madrid | Madrid | 28050 | Spain |
| FG001 |
| Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) |
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. |
| FG002 | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| FG003 | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. |
| FG004 | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| FG005 | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| FG006 | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| FG007 | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. |
| BG001 | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| BG002 | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| BG003 | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. |
| BG004 | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| BG005 | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| BG006 | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| BG007 | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
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| Primary | Maximum Tolerated Dose (MTD) - Part 1 | 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. | 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. | Posted | Number | mg | Part 1 Baseline up to Day 21 |
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| Primary | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Part 1 | 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. | Safety population: included participants who received at least 1 dose of the study medication. | Posted | Number | Percentage of Participants | Part 1 Baseline up to 28 days after last dose of study treatment |
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| Primary | Percentage of Participants With Objective Response - Part 2 | 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. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
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| Secondary | Best Overall Response - Part 1 | 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. | 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. | Posted | Number | Participants | Part 1 Baseline, every 6 weeks up to 6 months |
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| Secondary | Progression Free Survival (PFS) - Part 2 | 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"). | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
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| Secondary | Clinical Benefit Rate - Part 2 | 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. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
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| Secondary | Duration of Response (DR) - Part 2 | 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. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) - Part 2 | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 2 | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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| Secondary | Apparent Volume of Distribution (Vz/F) - Part 2 | 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. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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| Secondary | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] - Part 2 | AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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| Secondary | Apparent Oral Clearance (CL/F) - Part 2 | 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. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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| Secondary | Terminal-Phase Disposition Rate Constant (λz) - Part 2 | The terminal-phase disposition rate constant measured by a log-linear regression of the terminal mono exponential portion of the observed plasma concentrations. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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| Secondary | Plasma Decay Half-Life (t1/2) - Part 2 | 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. | Data was not analyzed because the study was prematurely terminated due to unfavorable risk benefit ratio of the study treatment. | Posted | 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1 |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. | 0 | 2 | 2 | 2 | ||
| EG001 | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. | 2 | 4 | 4 | 4 | ||
| EG002 | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. | 2 | 4 | 3 | 4 | ||
| EG003 | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. | 2 | 5 | 5 | 5 | ||
| EG004 | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. | 0 | 4 | 4 | 4 | ||
| EG005 | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. | 3 | 9 | 9 | 9 | ||
| EG006 | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. | 0 | 2 | 2 | 2 | ||
| EG007 | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. | 1 | 2 | 2 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA | Non-systematic Assessment |
| |
| Gastrointestinal obstruction | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Glioblastoma multiforme | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Non-systematic Assessment |
| |
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Non-systematic Assessment |
| |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA | Non-systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
|
Results are not provided because the study was terminated prior to part 2 due to unfavorable risk benefit ratio of the study treatment.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| ID | Term |
|---|---|
| C471992 | bosutinib |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
Not provided
Not provided
| Male |
|
| OG002 | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| OG003 | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. |
| OG004 | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| OG005 | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| OG006 | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| OG007 | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
|
|
|
| OG002 | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| OG003 | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 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. |
| OG004 | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| OG005 | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
| OG006 | Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | 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. |
| OG007 | Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | 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. |
|
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