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)

NCT ID: NCT01702558

Last Updated: 2021-01-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-03
• Study Completion Date: 2017-05-31

Brief Summary

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

Conditions

Breast Cancer; Gastric Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Capecitabine will be administered at de-escalating doses (starting from 750 mg/m\^2) to determine the MTD.

Trastuzumab emtansine (T-DM1)

Intervention Type: DRUG

Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.

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.

Group Type: EXPERIMENTAL

Trastuzumab emtansine (T-DM1)

Intervention Type: DRUG

Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.

Capecitabine

Intervention Type: DRUG

Capecitabine will be administered at the MTD determined in Cohort 1.

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.

Group Type: ACTIVE_COMPARATOR

Trastuzumab emtansine (T-DM1)

Intervention Type: DRUG

Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.

Capecitabine

Intervention Type: DRUG

Capecitabine will be administered at the MTD determined in Cohort 1.

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.

Group Type: EXPERIMENTAL

Trastuzumab emtansine (T-DM1)

Intervention Type: DRUG

Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.

Interventions

Capecitabine

Capecitabine will be administered at de-escalating doses (starting from 750 mg/m\^2) to determine the MTD.

Intervention Type: DRUG

Trastuzumab emtansine (T-DM1)

Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.

Intervention Type: DRUG

Trastuzumab emtansine (T-DM1)

Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.

Intervention Type: DRUG

Capecitabine

Capecitabine will be administered at the MTD determined in Cohort 1.

Intervention Type: DRUG

Other Intervention Names

Xeloda; Kadcyla,; RO5304020; Kadcyla,; RO5304020; Xeloda

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Fundacion Investigar

CABA, , Argentina

Centro Oncologico Riojano Integral (CORI)

La Rioja, , Argentina

Hospital Erasto Gaertner

Curitiba, Paraná, Brazil

Instituto Oncologico de Ribeirao Preto - INORP

Ribeirão Preto, São Paulo, Brazil

Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*

São José do Rio Preto, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

ICO Paul Papin; Oncologie Medicale.

Angers, , France

Centre Leon Berard; Departement Oncologie Medicale

Lyon, , France

Institut Paoli Calmettes; Oncologie Medicale

Marseille, , France

Institut Curie; Oncologie Medicale

Paris, , France

Ico Rene Gauducheau; Oncologie

Saint-Herblain, , France

Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.

Berlin, , Germany

Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie

Bielefeld, , Germany

Heinrich-Heine Universitätsklinik Düsseldorf

Düsseldorf, , Germany

Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH

Fulda, , Germany

Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie

Marburg, , Germany

Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)

München, , Germany

Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde

München, , Germany

Alexandras General Hospital of Athens; Oncology Department

Athens, , Greece

Univ General Hosp Heraklion; Medical Oncology

Heraklion, , Greece

University Hospital of Patras Medical Oncology

Pátrai, , Greece

Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica

Napoli, Campania, Italy

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico

Candiolo, Piedmont, Italy

Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia

Pontedera, Tuscany, Italy

Hospital da Luz; Departamento de Oncologia Medica

Lisbon, , Portugal

Hospital de Santa Maria; Servico de Oncologia Medica

Lisbon, , Portugal

IPO do Porto; Servico de Oncologia Medica

Porto, , Portugal

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Blokhin Cancer Research Center; Combined Treatment

Moscow, , Russia

City Clinical Oncology Hospital

Moscow, , Russia

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

Saint Petersburg, , Russia

City Oncology Dispensary

Saint Petersburg, , Russia

Bashkirian Republican Clinical Oncology Dispensary

Ufa, , Russia

Institute for Oncology and Radiology of Serbia; Medical Oncology

Belgrade, , Serbia

Clinical Centre Nis, Clinic for Oncology

Niš, , Serbia

Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A

Bratislava, , Slovakia

Fakultna nemocnica Trencín; Onkologicke odd.

Trenčín, , Slovakia

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Countries

Argentina; Brazil; Canada; France; Germany; Greece; Italy; Portugal; Russia; Serbia; Slovakia; Spain

References

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.

Reference Type: DERIVED

PMID: 32584367 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-001547-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO28230

Identifier Type: -

Identifier Source: org_study_id