A Study of Trastuzumab-MCC-DM1 (T-DM1) in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression - Full Text View

Sponsor:	Genentech
Information provided by (Responsible Party):	Genentech
ClinicalTrials.gov Identifier:	NCT00943670

Purpose

This is a multicenter, open-label, single-arm Phase II study designed to evaluate the effect of T-DM1 on the duration of corrected QT (QTc) interval in patients with HER2-positive locally advanced or metastatic breast cancer and to make preliminary assessments regarding the safety, tolerability, and efficacy of combined T-DM1 and pertuzumab in patients with early disease progression.

The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QTcF interval is the QT interval as calculated using Fridericia's correction; the QTcB interval is the QT interval as calculated using Bazett's correction.

Condition	Intervention	Phase
Metastatic Breast Cancer	Drug: pertuzumab Drug: trastuzumab-MCC-DM1	Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II, Open-Label Study to Evaluate Corrected QT Interval Effects of Trastuzumab-MCC-DM1 (T-DM1) in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer and to Evaluate the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression While Receiving T-DM1 Alone

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Trastuzumab Pertuzumab

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Baseline-adjusted QTcF [ Time Frame: At each post-baseline timepoint (Cycle 1, Day 1; Cycle 1 Day 8; Cycle 3, Day 1) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Baseline-adjusted QTcB [ Time Frame: At each post-baseline timepoint (Cycle 1, Day 1; Cycle 1 Day 8; Cycle 3, Day 1) ] [ Designated as safety issue: No ]
Baseline-adjusted heart rate, uncorrected QT interval, PR interval, and QRS duration [ Time Frame: At each post-baseline timepoint (Cycle 1, Day 1; Cycle 1 Day 8; Cycle 3, Day 1) ] [ Designated as safety issue: No ]
Objective response based on investigator assessment [ Time Frame: Confirmation of partial response (PR) or complete response (CR) ≥ 4 weeks after the criteria for response are first met ] [ Designated as safety issue: No ]
Duration of objective response based on investigator assessment [ Time Frame: Time from the first documented objective response to the time of first documented disease progression or death, whichever comes first ] [ Designated as safety issue: No ]

Enrollment:	51
Study Start Date:	July 2009
Study Completion Date:	August 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: pertuzumab Intravenous repeating dose Drug: trastuzumab-MCC-DM1 Intravenous repeating dose

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically documented, locally advanced, or metastatic breast cancer; measurable and/or non-measureable but evaluable disease is permitted
HER2-positive disease
History of prior trastuzumab therapy
Life expectancy ≥ 90 days as assessed by the investigator
Negative urine pregnancy test ≤ 72 hours prior to C1D1 for all women of childbearing potential
For patients of childbearing potential, agreement to use one highly effective form of contraception or two effective forms of contraception for the duration of the study treatment(s) and for 4 months after the last dose of T-DM1 or 6 months after the last dose of pertuzumab, if applicable

Exclusion Criteria:

Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy for the treatment of breast cancer within 2 weeks of the first study treatment
Prior T-DM1 or pertuzumab therapy
History of intolerance (such as Grade 3-4 infusion reaction) and/or adverse events related to trastuzumab
Grade ≥ 2 (based on NCI CTCAE v3) peripheral neuropathy at the time of or within 3 weeks prior to the first study treatment
Brain metastases that are untreated or progressive or have required any type of therapy, including radiation, surgery, and/or steroids, to control symptoms from brain metastases within 60 days prior to the first study treatment
History of cardiac disease, unstable angina, symptomatic CHF (Class ≥ II per the New York Heart Associate [NYHA] guidelines), myocardial infarction, or ventricular arrhythmia ≤ 6 months prior to Cycle 1, Day 1
Implantable pacemaker or automatic implantable cardioverter defibrillator
Congenital long QT syndrome or family history of long QT syndrome
Current uncontrolled hypertension
Current treatment with medications that alter cardiac conduction (e.g., digitalis, beta-blockers, or calcium channel blockers) or medications that are generally accepted to have a risk of causing torsades de pointes (TdP)
Current known active infection with HIV, hepatitis B virus, or hepatitis C virus
Major surgical procedure or significant traumatic injury within 28 days prior to first study treatment, or anticipation of the need for major surgery during the course of study treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943670

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Yu-Waye Chu, M.D.

Genentech

More Information

No publications provided

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00943670 History of Changes
Other Study ID Numbers:	TDM4688g
Study First Received:	July 19, 2009
Last Updated:	December 21, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

MBC
TDM1
Armed Herceptin
Herceptin
Trastuzumab emtansine

Additional relevant MeSH terms:

Breast Neoplasms
Disease Progression
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

Disease Attributes
Pathologic Processes
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012