Breast CancerPhase 2TRAXHER2NCT01702558
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)
A Phase 2 study testing Capecitabine and Trastuzumab emtansine (T-DM1) in people with Breast Cancer and Gastric Cancer, run by Hoffmann-La Roche at 40 sites in 12 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Gastric Cancer
- What is being tested?
- Capecitabine and Trastuzumab emtansine (T-DM1)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 40 sitesin 12 countries
- Study dates
- 3 Dec 2012to 31 May 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- Metastatic Breast Cancer
- Prior treatments before first study treatment:
- Investigational therapy within 28 days or 5 half-lives, whichever is longer
- Hormonal therapy within 14 days
- 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
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- Prior treatment with capecitabine
- History of severe or unexpected reactions to fluoropyrimidine or known hypersensitivity to fluorouracil
- Related capecitabine contraindications
- Treatment with sorivudine or chemically-related analogues
- Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- 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)
Trial locations and contacts
40 sites in 12 countries.
40 sites in 12 countries
Germany7 sites
Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
Berlin, 10117
Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie
Bielefeld, 33604
Heinrich-Heine Universitätsklinik Düsseldorf
Düsseldorf, 40225
Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH
Fulda, 36043
Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie
Marburg, 35043
Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)
München, 81675
Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde
München, 81675
Russia6 sites
Ivanovo Regional Oncology Dispensary
Ivanovo, 153040
Blokhin Cancer Research Center; Combined Treatment
Moscow, 115478
City Clinical Oncology Hospital
Moscow, 143423
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
Saint Petersburg, 197758
City Oncology Dispensary
Saint Petersburg
Bashkirian Republican Clinical Oncology Dispensary
Ufa, 450054
France5 sites
ICO Paul Papin; Oncologie Medicale.
Angers, 49055
Centre Leon Berard; Departement Oncologie Medicale
Lyon, 69373
Institut Paoli Calmettes; Oncologie Medicale
Marseille, 13273
Institut Curie; Oncologie Medicale
Paris, 75231
Ico Rene Gauducheau; Oncologie
Saint-Herblain, 44805
Brazil4 sites
Hospital Erasto Gaertner
Curitiba, Paraná, 81520-060
Instituto Oncologico de Ribeirao Preto - INORP
Ribeirão Preto, São Paulo, 14025-270
Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*
São José do Rio Preto, São Paulo, 15090-000
Instituto do Cancer do Estado de Sao Paulo - ICESP
São Paulo, São Paulo, 01246-000
Italy4 sites
Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
Candiolo, Piedmont, 10060
Istituto Europeo Di Oncologia
Milan, Lombardy, 20141
Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
Naples, Campania, 80131
Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia
Pontedera, Tuscany, 56025
Greece3 sites
Alexandras General Hospital of Athens; Oncology Department
Athens, 115 28
Univ General Hosp Heraklion; Medical Oncology
Heraklion, 711 10
University Hospital of Patras Medical Oncology
Pátrai, 265 04
Portugal3 sites
Hospital da Luz; Departamento de Oncologia Medica
Lisbon, 1500-650
Hospital de Santa Maria; Servico de Oncologia Medica
Lisbon, 1649-035
IPO do Porto; Servico de Oncologia Medica
Porto, 4200-072
Argentina2 sites
Fundacion Investigar
CABA, C1025ABI
Centro Oncologico Riojano Integral (CORI)
La Rioja, F5300COE
Serbia2 sites
Institute for Oncology and Radiology of Serbia; Medical Oncology
Belgrade, 11000
Clinical Centre Nis, Clinic for Oncology
Niš, 18000
Slovakia2 sites
Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A
Bratislava, 833 10
Fakultna nemocnica Trencín; Onkologicke odd.
Trenčín, 911 71
Canada1 site
British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: Phase I Study of the Combination of Trastuzumab Emtansine (T-DM1) and Capecitabine in HER2-Positive Metastatic Breast Cancer and HER2-Positive Locally Advanced/Metastatic Gastric Cancer Patients, Followed by a Randomized, Open-Label Phase II Study of Trastuzumab Emtansine and Capecitabine Versus Trastuzumab Emtansine Alone in HER2-Positive Metastatic Breast Cancer
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.
- Conditions
- Breast Cancer, Gastric Cancer
- Being tested
- Capecitabine, Trastuzumab emtansine (T-DM1)
- Medical subject headings
- Breast Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Xeloda
Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.
Trastuzumab emtansine (T-DM1)Drug
Also called Kadcyla,, RO5304020
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.
Trastuzumab emtansine (T-DM1)Drug
Also called Kadcyla,, RO5304020
Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.
CapecitabineDrug
Also called Xeloda
Capecitabine will be administered at the MTD determined in Cohort 1.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine | Experimental | 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. Receives: Drug: Capecitabine; Drug: Trastuzumab emtansine (T-DM1) |
| Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine | Experimental | 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. Receives: Drug: Trastuzumab emtansine (T-DM1); Drug: Capecitabine |
| Phase 2 (mBC): T-DM1 + Capecitabine | Active comparator | 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. Receives: Drug: Trastuzumab emtansine (T-DM1); Drug: Capecitabine |
| Phase 2 (mBC): T-DM1 | Experimental | 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. Receives: Drug: Trastuzumab emtansine (T-DM1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)
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 (%).
Measured: Continuously during Cycle 1 (up to 3 weeks)
Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 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%.
Measured: Continuously during Cycle 1 (up to 3 weeks)
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)
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.
Measured: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 1 (LA/mGC): Percentage of Participants With DLTs
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%.
Measured: Continuously during 3 weeks
Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW)
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%.
Measured: Continuously during 3 weeks
Secondary outcomes (29)
Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall)
Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine
Measured: 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
Trastuzumab was derived from trastuzumab emtansine.
Measured: 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 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine
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.
Measured: 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
Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) 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 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.
Measured: 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
Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) 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 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.
Measured: 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
Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)
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.
Measured: 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
Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)
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.
Measured: 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
Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)
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.
Measured: 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
Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1
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.
Measured: From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause
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.
Measured: Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants Who Died of Any Cause
Measured: Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Overall Survival (OS)
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.
Measured: Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1
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.
Measured: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall)
Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine
Measured: 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): Serum Concentration of Trastuzumab
Trastuzumab was derived from trastuzumab emtansine.
Measured: 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
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.
Measured: 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
Phase 1 (LA/mGC): AUC(0-inf) 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 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.
Measured: 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
Phase 1 (LA/mGC): t1/2 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 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.
Measured: 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
Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)
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.
Measured: 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
Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)
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.
Measured: 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
Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2012 (estimated)
- Study start3 Dec 2012
- Primary completion31 May 2017
- Study completion31 May 2017
Why it stopped: The sponsor decided to terminate study after 70% of participants had experienced a progression-free survival event.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 182 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01702558
- Sponsor's protocol ID
- MO28230
- Other IDs
- 2012-001547-46
- Acronym
- TRAXHER2
- Status last verified
- Jan 2021
- First submitted
- 4 Oct 2012
- Last updated
- 22 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Cortes J, Dieras V, Lorenzen S, Montemurro F, Riera-Knorrenschild J, Thuss-Patience P, Allegrini G, De Laurentiis M, Lohrisch C, Oravcova E, Perez-Garcia JM, Ricci F, Sakaeva D, Serpanchy R, Sufliarsky J, Vidal M, Irahara N, Wohlfarth C, Aout M, Gelmon K. Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial. JAMA Oncol. 2020 Aug 1;6(8):1203-1209. doi: 10.1001/jamaoncol.2020.1796.
PubMed 32584367
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Combination of Trastuzumab Emtansine (T-DM1) and Capecitabine in HER2-Positive Metastatic Breast Cancer and HER2-Positive Locally Advanced/Metastatic Gastric Cancer Patients, Followed by a Randomized, Open-Label Phase II Study of Trastuzumab Emtansine and Capecitabine Versus Trastuzumab Emtansine Alone in HER2-Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01702558
- Acronym / sponsor ID
- TRAXHER2 / MO28230
- Conditions
- Breast Cancer, Gastric Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to terminate study after 70% of participants had experienced a progression-free survival event.
- Enrolment
- 182 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 3 Dec 2012 (actual)
- Primary completion
- 31 May 2017 (actual)
- Study completion
- 31 May 2017 (actual)
- First posted
- 8 Oct 2012 (estimated)
- Results
- Posted 8 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine | Experimental | Drug: Capecitabine, Drug: 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 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine | Experimental | Drug: Trastuzumab emtansine (T-DM1), Drug: CapecitabineIn 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 + Capecitabine | Active comparator | Drug: Trastuzumab emtansine (T-DM1), Drug: CapecitabineIn 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 2 (mBC): T-DM1 | Experimental | Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (29 listed)
- Metastatic Breast Cancer
- Prior treatments before first study treatment:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineAlso: XelodaCapecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD. | Drug | Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine |
| Trastuzumab emtansine (T-DM1)Also: Kadcyla,, RO5304020Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks. | Drug | Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine, Phase 2 (mBC): T-DM1, Phase 2 (mBC): T-DM1 + Capecitabine |
| Trastuzumab emtansine (T-DM1)Also: Kadcyla,, RO5304020Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week. | Drug | Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine |
| CapecitabineAlso: XelodaCapecitabine will be administered at the MTD determined in Cohort 1. | Drug | Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine, Phase 2 (mBC): T-DM1 + Capecitabine |
Primary outcome
Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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%.
29 secondary outcomes
Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall)
Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine
Time frame: 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
Time frame: 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 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine
Time frame: 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
Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine
Time frame: 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
Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine
Time frame: 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
Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)
Time frame: 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
Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)
Time frame: 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
Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)
Time frame: 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
Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1
Time frame: From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause
Time frame: Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Percentage of Participants Who Died of Any Cause
Time frame: Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 2 (mBC): Overall Survival (OS)
Time frame: Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall)
Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1
Time frame: Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall)
Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine
Time frame: 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): Serum Concentration of Trastuzumab
Time frame: 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
Time frame: 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
Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine
Time frame: 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
Phase 1 (LA/mGC): t1/2 of Capecitabine
Time frame: 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
Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine)
Time frame: 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
Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine)
Time frame: 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
Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32584367Cortes J, Dieras V, Lorenzen S, Montemurro F, Riera-Knorrenschild J, Thuss-Patience P, Allegrini G, De Laurentiis M, Lohrisch C, Oravcova E, Perez-Garcia JM, Ricci F, Sakaeva D, Serpanchy R, Sufliarsky J, Vidal M, Irahara N, Wohlfarth C, Aout M, Gelmon K. Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial. JAMA Oncol. 2020 Aug 1;6(8):1203-1209. doi: 10.1001/jamaoncol.2020.1796.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
40 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine and Trastuzumab emtansine (T-DM1) in people with Breast Cancer and Gastric Cancer, run by Hoffmann-La Roche at 40 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Germany, Russia, France, Brazil, Italy and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Continuously during Cycle 1 (up to 3 weeks)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01702558, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.