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) (TRAXHER2)

January 19, 2021 updated by: Hoffmann-La Roche

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

182

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Caba, Argentina, C1025ABI
        • Fundación Investigar
      • La Rioja, Argentina, F5300COE
        • Centro Oncologico Riojano Integral (CORI)
  • Brazil
    • PR
      • Curitiba, PR, Brazil, 81520-060
        • Hospital Erasto Gaertner
    • SP
      • Ribeirao Preto, SP, Brazil, 14025-270
        • Instituto Oncológico de Ribeirão Preto - InORP
      • Sao Jose do Rio Preto, SP, Brazil, 15090-000
        • Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*
      • Sao Paulo, SP, Brazil, 01246-000
        • Instituto do Cancer do Estado de Sao Paulo - ICESP
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
  • France
      • Angers, France, 49055
        • ICO Paul Papin; Oncologie Medicale.
      • Lyon, France, 69373
        • Centre Leon Berard; Departement Oncologie Medicale
      • Marseille, France, 13273
        • Institut Paoli Calmettes; Oncologie Medicale
      • Paris, France, 75231
        • Institut Curie; Oncologie Medicale
      • Saint Herblain, France, 44805
        • Ico Rene Gauducheau; Oncologie
  • Germany
      • Berlin, Germany, 10117
        • Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
      • Bielefeld, Germany, 33604
        • Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie
      • Düsseldorf, Germany, 40225
        • Heinrich-Heine Universitätsklinik Düsseldorf
      • Fulda, Germany, 36043
        • Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH
      • Marburg, Germany, 35043
        • Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie
      • München, Germany, 81675
        • Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde
      • München, Germany, 81675
        • Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)
  • Greece
      • Athens, Greece, 115 28
        • Alexandras General Hospital of Athens; Oncology Department
      • Heraklion, Greece, 711 10
        • Univ General Hosp Heraklion; Medical Oncology
      • Patras, Greece, 265 04
        • University Hospital of Patras Medical Oncology
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
    • Lombardia
      • Milano, Lombardia, Italy, 20141
        • Istituto Europeo di Oncologia
    • Piemonte
      • Candiolo, Piemonte, Italy, 10060
        • Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
    • Toscana
      • Pontedera, Toscana, Italy, 56025
        • Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia
  • Portugal
      • Lisboa, Portugal, 1500-650
        • Hospital da Luz; Departamento de Oncologia Medica
      • Lisboa, Portugal, 1649-035
        • Hospital de Santa Maria; Servico de Oncologia Medica
      • Porto, Portugal, 4200-072
        • IPO do Porto; Servico de Oncologia Medica
  • Russian Federation
      • Ivanovo, Russian Federation, 153040
        • Ivanovo Regional Oncology Dispensary
      • Moscow, Russian Federation, 143423
        • City Clinical Oncology Hospital
      • Moscow, Russian Federation, 115478
        • Blokhin Cancer Research Center; Combined Treatment
      • Saint-Petersburg, Russian Federation, 197758
        • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
      • St Petersburg, Russian Federation
        • City Oncology Dispensary
      • UFA, Russian Federation, 450054
        • Bashkirian Republican Clinical Oncology Dispensary
  • Serbia
      • Belgrade, Serbia, 11000
        • Institute for Oncology and Radiology of Serbia; Medical Oncology
      • Nis, Serbia, 18000
        • Clinical Centre Nis, Clinic for Oncology
  • Slovakia
      • Bratislava, Slovakia, 833 10
        • Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A
      • Trencin, Slovakia, 911 71
        • Fakultna nemocnica Trencín; Onkologicke odd.
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Univ Vall d'Hebron; Servicio de Oncologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Phase 1 (mBC) Cohort 1: T-DM1 + 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.
Drug: Capecitabine
Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.
Other Names:
  • Xeloda
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Capecitabine
Capecitabine will be administered at the MTD determined in Cohort 1.
Other Names:
  • Xeloda
EXPERIMENTAL: Phase 1 (LA/mGC) Cohort 2: T-DM1 + 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.
Drug: Capecitabine
Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.
Other Names:
  • Xeloda
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Capecitabine
Capecitabine will be administered at the MTD determined in Cohort 1.
Other Names:
  • Xeloda
ACTIVE_COMPARATOR: Phase 2 (mBC): T-DM1 + 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.
Drug: Capecitabine
Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.
Other Names:
  • Xeloda
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Capecitabine
Capecitabine will be administered at the MTD determined in Cohort 1.
Other Names:
  • Xeloda
EXPERIMENTAL: Phase 2 (mBC): 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.
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.
Other Names:
  • RO5304020
  • Kadcyla,
Drug: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.
Other Names:
  • RO5304020
  • Kadcyla,

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 (%).
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)
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%.
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)
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.
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
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%.
Continuously during 3 weeks
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%.
Continuously during 3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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)
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)
Trastuzumab was derived from 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 (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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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)
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.
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)
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.
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)
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.
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)
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.
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)
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.
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)
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.
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)
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.
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)
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.
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)
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.
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)
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)
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.
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)
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.
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)
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)
Trastuzumab was derived from 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
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

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General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 3, 2012

Primary Completion (ACTUAL)

May 31, 2017

Study Completion (ACTUAL)

May 31, 2017

Study Registration Dates

First Submitted

October 4, 2012

First Submitted That Met QC Criteria

October 5, 2012

First Posted (ESTIMATE)

October 8, 2012

Study Record Updates

Last Update Posted (ACTUAL)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 19, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MO28230
  • 2012-001547-46 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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