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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01702558
First received: October 4, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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/me tastatic gastric cancer using a Phase I design, followed by a randomized, open-l abel Phase II study to explore the efficacy and safety of the combination of Kad cyla and capecitabine compared with Kadcyla in metastatic breast cancer patients The anticipated time on study treatment is until disease progression, intolera ble toxicity, or withdrawal of consent.


Condition Intervention Phase
Breast Cancer, Gastric Cancer
Drug: trastuzumab emtansine [Kadcyla]
Drug: capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Phase I: Maximum tolerated dose (MTD) of the combination of Kadcyla and capecitabine in metastatic gastric cancer [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I: Maximum tolerated dose (MTD) of the combination of Kadcyla and capecitabine in metastatic breast cancer [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Overall response rate (ORR) in metastatic breast cancer, based on best overall response (BOR) rate according to RECIST v.1.1 [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase II - Safety: incidence of adverse events [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I - Pharmacokinetics: Serum concentration of trastuzumab emtansine [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I - Pharmacokinetics: Serum concentration of trastuzumab [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I - Pharmacokinetics: Plasma concentration of DM1 [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I - Pharmacokinetics: Plasma concentration of capecitabine [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I - Pharmacokinetics: Plasma concentration of 5-fluorouracil [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase I - Safety: incidence of adverse events of the combination of Kadcyla and capecitabine [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: ORR in metastatic gastric cancer, based on BOR rate according to RECIST v.1.1 [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Time to response according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Duration of response according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Time to progression according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Time to treatment failure according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Progression free survival according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Clinical benefit rate according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Overall survival according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 235
Study Start Date: December 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: Metastatic Breast Cancer Cohort Drug: trastuzumab emtansine [Kadcyla]
3.6 mg/kg intravenously every 3 weeks until disease progression, intolerable toxicity, withdrawal of consent
Drug: capecitabine
650-750 mg/m2 twice daily
Experimental: Phase I: Metastatic Gastric Cancer Cohort Drug: trastuzumab emtansine [Kadcyla]
2.4 mg/kg intravenously every 3 weeks until disease progression, intolerable toxicity, withdrawal of consent
Drug: capecitabine
650-750 mg/m2 twice daily
Experimental: Phase II: Kadcyla + capecitabine Drug: trastuzumab emtansine [Kadcyla]
3.6 mg/kg intravenously every 3 weeks
Drug: capecitabine
Dosed at maximum tolerated dose (MTD) established in Phase I
Active Comparator: Phase II: Kadcyla Drug: trastuzumab emtansine [Kadcyla]
3.6 mg/kg intravenously every 3 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 </= 28 days or 5 half lives, whichever is longest
    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 </= 14 days before first study drug administration

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702558

Contacts
Contact: Reference Study ID Number: MO28230 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
Canada, British Columbia
Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
France
Recruiting
Paris, France, 75231
Greece
Not yet recruiting
Athens, Greece, 11528
Not yet recruiting
Heraklion, Greece, 711 10
Not yet recruiting
Patras, Greece, 265 00
Spain
Recruiting
Barcelona, Spain, 08035
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01702558     History of Changes
Other Study ID Numbers: MO28230, 2012-001547-46
Study First Received: October 4, 2012
Last Updated: August 11, 2014
Health Authority: Spain: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Stomach Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Trastuzumab
Capecitabine
Ado-trastuzumab emtansine
Fluorouracil
Maytansine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 18, 2014