A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Patients With Breast Cancer or Gastric Cancer

This study is currently recruiting participants.
Verified April 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: April 7, 2014
Last verified: April 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 or locally advanced or 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.


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
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 OR METASTATIC GASTRIC CANCER PATIENTS FOLLOWED BY A RANDOMIZED, OPEN-LABEL PHASE II STUDY OF T-DM1 AND CAPECITABINE VERSUS T-DM1 ALONE IN HER2-POSITIVE METASTATIC BREAST CANCER

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 [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II: Overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 I: Overall response rate according to RECIST [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Phase II - Safety: incidence of adverse events [ 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: 130
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

  • ECOG performance status of 0, 1, or 2
  • Adequate blood cell count
  • Adequate liver, renal and cardiac function
  • Histologically or cytologically confirmed breast cancer
  • Confirmed HER2-positive disease
  • Metastatic breast cancer with at least one measurable lesion according to RECIST v. 1.1
  • Disease progression on at least one regimen containing trastuzumab and chemotherapy
  • 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
  • Histologically or cytologically confirmed metastatic gastric cancer or locally advanced gastric cancer
  • HER2-positive tumor (primary tumor or metastatic lesion)
  • Inoperable locally advanced or metastatic gastric cancer

Exclusion Criteria:

  • Prior treatments before first study treatment:

    1. Investigational therapy within </= 28 days or 5 half lives, whatever 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 prior trastuzumab emtansine
  • Prior treatment with capecitabine
  • History of severe and unexpected reactions to fluoropyrimidine or with known hypersensitivity to fluorouracil
  • Related capecitabine contraindications
  • 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 of first study drug administration
  • Current peripheral neuropathy of Grade >/= 3 per 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 requiring current 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 within 14 days prior to first study drug administration
  • No signs or symptoms of dihydropyrimidine dehydrogenase (DPD) deficiency
  Contacts and Locations
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
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: April 7, 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
Fluorouracil
Maytansine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on April 23, 2014