A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (mBC) or HER2-Positive Locally Advanced/Metastatic Gastric Cancer (LA/mGC)

Phase 2

Terminated

Conditions: Breast Cancer
Gastric Cancer

Interventions: Drug: Trastuzumab emtansine (T-DM1)
Drug: Capecitabine

Registration Number: NCT01702558

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This multicenter study will assess the maximum tolerated dose (MTD) of capecitabine in combination with Kadcyla (trastuzumab emtansine) in participants with HER2-positive mBC or HER2-positive LA/mGC using a Phase 1 design, followed by a randomized, open-label Phase 2 part to explore the efficacy and safety of the combination of Kadcyla and capecitabine compared with Kadcyla alone in participants with mBC. The anticipated time on study treatment is until disease progression, intolerable toxicity, withdrawal of consent, or study end.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 182

Inclusion Criteria

Metastatic Breast Cancer

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Adequate blood cell count
Adequate liver, renal, and cardiac function
Life expectancy greater than or equal to (>/=) 12 weeks
Histologically or cytologically confirmed breast cancer
Confirmed HER2-positive disease, defined as immunohistochemistry (IHC) 3+ or in situ hybridization (ISH)-positive
mBC with at least one measurable lesion according to RECIST v1.1
Disease progression on at least one prior regimen containing trastuzumab and chemotherapy either separately or in combination; participants may be eligible to receive study therapy in first-line setting if trastuzumab and chemotherapy were given in the neoadjuvant/adjuvant setting
Participant must have recovered from previous treatments

Locally Advanced/Metastatic Gastric Cancer

ECOG performance status of 0, 1, or 2
Adequate blood cell count
Adequate liver, renal, and cardiac function
Life expectancy >/= 12 weeks
Histologically or cytologically confirmed LA/mGC
HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ or IHC 2+ and ISH-positive
Inoperable LA/mGC

Exclusion Criteria

Metastatic Breast Cancer

Prior treatments before first study treatment:
1. Investigational therapy within 28 days or 5 half-lives, whichever is longer
2. Hormonal therapy within 14 days
3. Trastuzumab within 21 days
Prior treatment with trastuzumab emtansine or prior enrollment in a trastuzumab emtansine-containing study, regardless of whether the patient received trastuzumab emtansine
Prior treatment with capecitabine
History of severe or unexpected reactions to fluoropyrimidine or known hypersensitivity to fluorouracil
Related capecitabine contraindications
1. Treatment with sorivudine or chemically-related analogues
2. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
3. Complete absence of dihydropyrimidine dehydrogenase (DPD) activity
History of intolerance or hypersensitivity to trastuzumab or murine proteins or any product component
History of exposure to high cumulative doses of anthracyclines
Brain metastases that are symptomatic or require radiation, surgery, or steroid therapy to control symptoms within 28 days before study drug
Current peripheral neuropathy of Grade >/=3
History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome
Current unstable ventricular arrhythmia requiring treatment
History of symptomatic congestive heart failure (CHF)
History of myocardial infarction or unstable angina within 6 months prior to study drug
History of left ventricular ejection fraction (LVEF) less than (<) 40% or symptomatic CHF with previous trastuzumab treatment
Severe dyspnea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy
Clinically significant malabsorption syndrome or inability to take oral medication
Current severe, uncontrolled systemic disease (such as clinically significant cardiovascular, pulmonary, or metabolic disease)
Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during study treatment
Current known active infection with human immunodeficiency virus (HIV) or hepatitis B or C
Lapatinib within 14 days before study drug

Locally Advanced/Metastatic Gastric Cancer

Same as above, with addition of previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrollment into the study)

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine	Trastuzumab emtansine (T-DM1)	In Phase 1, Cohort 1 participants (with mBC) will receive trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 \[on Day 2 for Cycle 1\] of each 21-day cycle) along with capecitabine at de-escalating dose levels (starting from 750 milligrams per meter squared \[mg/m\^2\]) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, or study end.
Phase 2 (mBC): T-DM1 + Capecitabine	Trastuzumab emtansine (T-DM1)	In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at MTD via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.
Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine	Capecitabine	In Phase 1, Cohort 2 participants (with LA/mGC) will receive trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (on Day 2 of first week) of every week along with capecitabine at MTD (determined in Cohort 1) via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.
Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine	Trastuzumab emtansine (T-DM1)	In Phase 1, Cohort 2 participants (with LA/mGC) will receive trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (on Day 2 of first week) of every week along with capecitabine at MTD (determined in Cohort 1) via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.
Phase 2 (mBC): T-DM1	Trastuzumab emtansine (T-DM1)	In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, or study end.
Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine	Capecitabine	In Phase 1, Cohort 1 participants (with mBC) will receive trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 \[on Day 2 for Cycle 1\] of each 21-day cycle) along with capecitabine at de-escalating dose levels (starting from 750 milligrams per meter squared \[mg/m\^2\]) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, or study end.
Phase 2 (mBC): T-DM1 + Capecitabine	Capecitabine	In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at MTD via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end.

Primary Outcome Measures

Name	Time	Method
Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)	Continuously during Cycle 1 (up to 3 weeks)	A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (\>) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (\<) 1000 cells/millimeter cube (mm\^3); Grade greater than or equal to (\>/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase \[DPD\] deficiency only for DL 1); any other Grade \>/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for \>14 days (\>7 days for DL 1); for DL -1 only: \<14 full doses of capecitabine; Cycle 2 dose level \<100 percent (%).
Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks)	Continuously during Cycle 1 (up to 3 weeks)	MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting \>7 consecutive days; febrile neutropenia with ANC \<1000 cells/mm\^3; Grade \>/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade \>/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for \>14 days (\>7 days for DL 1); for DL -1 only: \<14 full doses of capecitabine; Cycle 2 dose level \<100%.
Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to \<10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as \>/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach.
Phase 1 (LA/mGC): Percentage of Participants With DLTs	Continuously during 3 weeks	A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting \>7 consecutive days; febrile neutropenia with ANC \<1000 cells/mm\^3; Grade \>/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade \>/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for \>14 days; \<14 full doses of capecitabine; Cycle 2 dose level \<100%.
Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW)	Continuously during 3 weeks	MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting \>7 consecutive days; febrile neutropenia with ANC \<1000 cells/mm\^3; Grade \>/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade \>/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for \>14 days; \<14 full doses of capecitabine; Cycle 2 dose level \<100%.

Secondary Outcome Measures

Name	Time	Method
Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine	Pre-trastuzumab emtansine dose (0 hour [h]) on Day 1 Cycle 2; 15-30 minutes (min) after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)
Phase 1 (mBC): Serum Concentration of Trastuzumab	Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)	Trastuzumab was derived from trastuzumab emtansine.
Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1	Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to \<10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as \>/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.
Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1	Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method.
Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1	Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method.
Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1	Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method.
Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1	Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to \<10 mm for nodal TLs/non-TLs; and no new lesions. PR: \>/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach.
Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1	Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to \<10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as \>/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.
Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause	Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.
Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1	Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to \<10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as \>/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions.
Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine	Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)
Phase 1 (LA/mGC): Cmax of Capecitabine	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation.
Phase 1 (LA/mGC): t1/2 of Capecitabine	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1	From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to \<10 mm for nodal TLs/non-TLs; and no new lesions. PR: \>/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method.
Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1	Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.
Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1	Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)	Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as \>/=20% relative increase with \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs.
Phase 2 (mBC): Percentage of Participants Who Died of Any Cause	Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Overall Survival (OS)	Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)	OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients.
Phase 1 (LA/mGC): Serum Concentration of Trastuzumab	Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days)	Trastuzumab was derived from trastuzumab emtansine.
Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.
Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)	Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1	5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation.

Trial Locations

Locations (40): Hospital Erasto Gaertner
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Curitiba, PR, Brazil
Instituto Oncologico de Ribeirao Preto - INORP
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Ribeirao Preto, SP, Brazil
Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*
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Sao Jose do Rio Preto, SP, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
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Sao Paulo, SP, Brazil
Centre Leon Berard; Departement Oncologie Medicale
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Lyon, France
Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
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Berlin, Germany
Ico Rene Gauducheau; Oncologie
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Saint Herblain, France
Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie
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Bielefeld, Germany
Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie
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Marburg, Germany
Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
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Napoli, Campania, Italy
Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
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Candiolo, Piemonte, Italy
Istituto Europeo Di Oncologia
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Milano, Lombardia, Italy
Hospital da Luz; Departamento de Oncologia Medica
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Lisboa, Portugal
Hospital de Santa Maria; Servico de Oncologia Medica
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Lisboa, Portugal
IPO do Porto; Servico de Oncologia Medica
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Porto, Portugal
Ivanovo Regional Oncology Dispensary
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Ivanovo, Russian Federation
Blokhin Cancer Research Center; Combined Treatment
🇷🇺
Moscow, Russian Federation
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
🇷🇺
Saint-Petersburg, Russian Federation
City Clinical Oncology Hospital
🇷🇺
Moscow, Russian Federation
Clinical Centre Nis, Clinic for Oncology
🇷🇸
Nis, Serbia
City Oncology Dispensary
🇷🇺
St Petersburg, Russian Federation
Bashkirian Republican Clinical Oncology Dispensary
🇷🇺
UFA, Russian Federation
Institute for Oncology and Radiology of Serbia; Medical Oncology
🇷🇸
Belgrade, Serbia
Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A
🇸🇰
Bratislava, Slovakia
Fakultna nemocnica Trencín; Onkologicke odd.
🇸🇰
Trencin, Slovakia
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸
Barcelona, Spain
Fundacion Investigar
🇦🇷
Caba, Argentina
Centro Oncologico Riojano Integral (CORI)
🇦🇷
La Rioja, Argentina
British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
Institut Curie; Oncologie Medicale
🇫🇷
Paris, France
Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH
🇩🇪
Fulda, Germany
Heinrich-Heine Universitätsklinik Düsseldorf
🇩🇪
Düsseldorf, Germany
Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)
🇩🇪
München, Germany
ICO Paul Papin; Oncologie Medicale.
🇫🇷
Angers, France
Institut Paoli Calmettes; Oncologie Medicale
🇫🇷
Marseille, France
Alexandras General Hospital of Athens; Oncology Department
🇬🇷
Athens, Greece
Univ General Hosp Heraklion; Medical Oncology
🇬🇷
Heraklion, Greece
University Hospital of Patras Medical Oncology
🇬🇷
Patras, Greece
Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde
🇩🇪
München, Germany
Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia
🇮🇹
Pontedera, Toscana, Italy

A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (mBC) or HER2-Positive Locally Advanced/Metastatic Gastric Cancer (LA/mGC)

Recruitment & Eligibility

Study & Design

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