A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Patients With HER2-Positive Metastatic Breast Cancer and Patients With HER2-Positive Locally Advanced / Metastatic Gastric Cancer
Conditions
Breast Cancer, Gastric Cancer
Conditions: official terms
Stomach Neoplasms
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: capecitabine Type: Drug
Name: capecitabine Type: Drug
Name: trastuzumab emtansine [Kadcyla] Type: Drug
Name: trastuzumab emtansine [Kadcyla] Type: Drug
Name: trastuzumab emtansine [Kadcyla] Type: Drug
Overall Status
Recruiting
Summary
This multicenter study will assess the maximum tolerated dose of capecitabine in combination with Kadcyla (trastuzumab emtansine) in patients with HER2-positive metastatic breast cancer and in patients with HER2-positive locally advanced/metastatic gastric cancer using a Phase I design, followed by a randomized, open-label Phase II study to explore the efficacy and safety of the combination of Kadcyla and capecitabine compared with Kadcyla in metastatic breast cancer patients. The anticipated time on study treatment is until disease progression, intolerable toxicity, or withdrawal of consent.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

Metastatic Breast Cancer Patients

- Eastern Cooperative Oncology Group (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 breast cancer

- Confirmed HER2-positive disease, defined as immunohistochemistry (IHC) 3+ or in situ hybridization (ISH) positive

- Metastatic breast cancer with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1

- Disease progression on at least one prior regimen containing trastuzumab and chemotherapy either separately or in combination

- Patients must have recovered from previous treatments

Metastatic Gastric Cancer Patients

- 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 metastatic gastric cancer or locally advanced gastric cancer

- HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ or IHC 2+ and ISH+

- Inoperable locally advanced or metastatic gastric cancer

Exclusion Criteria:

Metastatic Breast Cancer Patients

- Prior treatments before first study treatment:

1. Investigational therapy within
2. Hormonal therapy within 14 days

3. Trastuzumab within 21 days

- 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 its chemically-related analogues, such as brivudine

2. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

3. Signs or symptoms suggesting that the patient has dihydropyrimidine dehydrogenase (DPD) deficiency

- History of intolerance or hypersensitivity to trastuzumab or murine proteins or any product component

- History of exposure to cumulative doses of anthracyclines

- Brain metastases that are symptomatic, or require any radiation, surgery, or steroid therapy to control their symptoms within 28 days before first study drug administration

- Current peripheral neuropathy of Grade >/= 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0

- 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 as those mentioned above

- Current unstable ventricular arrhythmia requiring treatment

- History of symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] Classes II-IV)

- History of myocardial infarction or unstable angina within 6 months prior to first study drug administration

- History of a decrease in LVEF to < 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 (e.g., 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 the course of study treatment

- Current known active infection with HIV, hepatitis B, and/or hepatitis C virus

- Lapatinib
Metastatic Gastric Cancer Patients: same as above, and:

- 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)
Locations
Caba, Argentina
Status: Not yet recruiting
La Rioja, Argentina
Status: Recruiting
Curitiba, PR, Brazil
Status: Not yet recruiting
Ribeirao Preto, SP, Brazil
Status: Not yet recruiting
Sao Jose do Rio Preto, SP, Brazil
Status: Not yet recruiting
Sao Paulo, SP, Brazil
Status: Not yet recruiting
Vancouver, British Columbia, Canada
Status: Recruiting
Angers, France
Status: Active, not recruiting
Lyon, France
Status: Recruiting
Marseille, France
Status: Recruiting
Paris, France
Status: Recruiting
Saint Herblain, France
Status: Recruiting
Berlin, Germany
Status: Recruiting
Bielefeld, Germany
Status: Recruiting
Düsseldorf, Germany
Status: Not yet recruiting
Fulda, Germany
Status: Recruiting
Leipzig, Germany
Status: Not yet recruiting
Lübeck, Germany
Status: Recruiting
Marburg, Germany
Status: Recruiting
München, Germany
Status: Recruiting
Troisdorf, Germany
Status: Recruiting
Athens, Greece
Status: Recruiting
Heraklion, Crete, Greece
Status: Recruiting
Patras, Greece
Status: Recruiting
Napoli, Campania, Italy
Status: Recruiting
Milano, Lombardia, Italy
Status: Recruiting
Candiolo, Piemonte, Italy
Status: Recruiting
Pontedera, Toscana, Italy
Status: Recruiting
Negrar, Veneto, Italy
Status: Recruiting
Lisboa, Portugal
Status: Recruiting
Lisboa, Portugal
Status: Recruiting
Porto, Portugal
Status: Active, not recruiting
Ivanovo, Russian Federation
Status: Recruiting
Moscow, Russian Federation
Status: Recruiting
Moscow, Russian Federation
Status: Not yet recruiting
Orenburg, Russian Federation
Status: Recruiting
Saint-Petersburg, Russian Federation
Status: Recruiting
St Petersburg, Russian Federation
Status: Recruiting
UFA, Russian Federation
Status: Recruiting
Belgrade, Serbia
Status: Not yet recruiting
Nis, Serbia
Status: Not yet recruiting
Banská Bystrica, Slovakia
Status: Recruiting
Bratislava, Slovakia
Status: Recruiting
Trencin, Slovakia
Status: Recruiting
Barcelona, Spain
Status: Active, not recruiting
Start Date
December 2012
Completion Date
January 2017
Sponsors
Hoffmann-La Roche
Source
Hoffmann-La Roche
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page