Continued HER2 Suppression With Lapatinib Plus Trastuzumab Versus Trastuzumab Alone

NCT ID: NCT00968968

Last Updated: 2019-06-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-20
• Study Completion Date: 2018-03-30

Brief Summary

This was a randomized, open-label, multi-center Phase III study evaluating the efficacy and safety of lapatinib in combination with trastuzumab versus trastuzumab alone as continued HER2 suppression therapy in women with HER2-positive metastatic breast cancer (MBC). Eligible subjects should have completed 12 to 24 weeks of first- or second-line treatment with trastuzumab plus chemotherapy, experienced either complete disappearance of all metastatic lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions, and been indicated to continue to receive trastuzumab alone as maintenance therapy. Eligible subjects who entered the LPT112515 study on first-line treatment should not have known history of central nervous system (CNS) metastases; subjects who entered the study on second-line treatment should not have known history of CNS metastases or have stable (asymptomatic and off steroids ≥3 months) CNS metastases. The primary objective of this study was to compare progression-free survival (PFS) in subjects with HER2-positive MBC randomized to receive treatment with lapatinib plus trastuzumab versus those randomized to receive trastuzumab alone. The secondary objectives included overall survival, clinical benefit response rate (CR, PR or SD ≥24 weeks) and the qualitative and quantitative adverse event profile of the 2 treatment arms. It was estimated that 280 subjects (140 per group) would be required to observe 193 PFS events.

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Lapatinib plus Trastuzumab

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

Oral Lapatinib 1000 mg once daily. Lapatinib was a small molecule, reversible inhibitor targeting HER2 tyrosine kinase receptor.

Trastuzumab

Intervention Type: BIOLOGICAL

IV Trastuzumab 6 mg/kg every three weeks. Trastuzumab was a humanized, monoclonal antibody directed against the extracellular domain of the HER2 tyrosine kinase receptor.

Arm 2: Trastuzumab

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: BIOLOGICAL

IV Trastuzumab 6 mg/kg every three weeks. Trastuzumab was a humanized, monoclonal antibody directed against the extracellular domain of the HER2 tyrosine kinase receptor.

Interventions

Lapatinib

Oral Lapatinib 1000 mg once daily. Lapatinib was a small molecule, reversible inhibitor targeting HER2 tyrosine kinase receptor.

Intervention Type: DRUG

Trastuzumab

IV Trastuzumab 6 mg/kg every three weeks. Trastuzumab was a humanized, monoclonal antibody directed against the extracellular domain of the HER2 tyrosine kinase receptor.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Signed the informed consent form (ICF)
• Female, ≥18 years of age
• Histologically verified breast cancer with distant metastases (metastatic breast cancer)
• Documentation of HER2 overexpression or gene amplification in the invasive component of either the primary tumor or metastatic disease site defined as:
• 3+ by IHC and/or
• HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH HER2 gene copies to chromosome 17 signal ratio of ≥2.0]
• Completed 12 to 24 weeks of first- or second-line treatment with trastuzumab in combination with chemotherapy
• Either complete disappearance of all lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions
• Documentation of lesion response during the course of therapy received prior to randomization (i.e., improvement or no worsening of tumor burden; the absence of new lesions)
• Measurable disease is not required for study participation
• No known or suspected (associated neurological signs and symptoms) brain metastases (including leptomeningeal involvement)
• Stable brain metastasis (defined as asymptomatic and off steroids ≥3 months) are permitted in subjects on second-line treatment (completed 12-24 weeks of second-line treatment with trastuzumab plus chemotherapy)
• Baseline of Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA)
• Completion of screening assessments
• Have adequate marrow and organ function

Exclusion Criteria

• History of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer (basal or squamous) are eligible
• Eastern Cooperative Oncology Group (ECOG) Performance Status >2
• Concurrent anti-cancer treatment, except anti-hormonal therapy for subjects with hormone receptor positive breast cancer
• Concurrent treatment with an investigational agent
• Prior treatment with anti-HER2 therapy, except trastuzumab or lapatinib
• Concurrent treatment with protocol-defined prohibited medications (refer to protocol for details)
• Serious cardiac illness or medical condition including but not confined to:
• Uncontrolled arrhythmias
• Uncontrolled or symptomatic angina
• History of congestive heart failure (CHF)
• Myocardial infarction <6 months from study entry
• Acute or current active (requiring anti-viral therapy) hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)
• Women of childbearing potential, including women whose last menstrual period was <12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during the study treatment period. Adequate contraception includes intra-uterine device, barrier methods with spermicide, or oral contraceptives (unless clinically contraindicated for the subject population or per local practice, refer to protocol for further details)
• Pregnant or lactating females
• Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients that, in the opinion of the Investigator or GSK medical monitor , contra-indicates participation

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

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Chandler, Arizona, United States

Novartis Investigative Site

Flagstaff, Arizona, United States

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Gilbert, Arizona, United States

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Mesa, Arizona, United States

Novartis Investigative Site

Mesa, Arizona, United States

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Sedona, Arizona, United States

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Tucson, Arizona, United States

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Bakersfield, California, United States

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Beverly Hills, California, United States

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Fullerton, California, United States

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La Jolla, California, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Pablo, California, United States

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Santa Maria, California, United States

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Hollywood, Florida, United States

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Hudson, Florida, United States

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New Port Richey, Florida, United States

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Augusta, Georgia, United States

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Augusta, Georgia, United States

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Dublin, Georgia, United States

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Arlington Heights, Illinois, United States

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Chicago, Illinois, United States

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Evanston, Illinois, United States

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Glenview, Illinois, United States

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Highland Park, Illinois, United States

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Joliet, Illinois, United States

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Niles, Illinois, United States

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Peoria, Illinois, United States

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Peoria, Illinois, United States

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Peoria, Illinois, United States

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Skokie, Illinois, United States

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Winfield, Illinois, United States

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Goshen, Indiana, United States

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Mishawaka, Indiana, United States

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Columbia, Maryland, United States

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Silver Spring, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Brownstown, Michigan, United States

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Dearborn, Michigan, United States

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Detroit, Michigan, United States

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West Bloomfield, Michigan, United States

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Burnsville, Minnesota, United States

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Coon Rapids, Minnesota, United States

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Edina, Minnesota, United States

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Fridley, Minnesota, United States

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Maplewood, Minnesota, United States

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Minneapolis, Minnesota, United States

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Saint Paul, Minnesota, United States

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Woodbury, Minnesota, United States

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Columbia, Missouri, United States

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Jefferson City, Missouri, United States

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Billings, Montana, United States

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Henderson, Nevada, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Cary, North Carolina, United States

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Elizabeth City, North Carolina, United States

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Greensboro, North Carolina, United States

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Raleigh, North Carolina, United States

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Raleigh, North Carolina, United States

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Washington, North Carolina, United States

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Abington, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Radnor, Pennsylvania, United States

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Abilene, Texas, United States

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Beaumont, Texas, United States

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Bedford, Texas, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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El Paso, Texas, United States

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Fort Worth, Texas, United States

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Fort Worth, Texas, United States

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Garland, Texas, United States

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Grapevine, Texas, United States

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Houston, Texas, United States

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Kerrville, Texas, United States

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Odessa, Texas, United States

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Plano, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Layton, Utah, United States

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Murray, Utah, United States

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Provo, Utah, United States

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Salt Lake City, Utah, United States

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Salt Lake City, Utah, United States

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Sandy City, Utah, United States

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Arlington, Virginia, United States

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Chesapeake, Virginia, United States

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Fairfax, Virginia, United States

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Gainesville, Virginia, United States

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Hampton, Virginia, United States

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Leesburg, Virginia, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Virginia Beach, Virginia, United States

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Williamsburg, Virginia, United States

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Edmonds, Washington, United States

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Federal Way, Washington, United States

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Gig Harbor, Washington, United States

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Lakewood, Washington, United States

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Puyallup, Washington, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Tacoma, Washington, United States

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Halifax, Nova Scotia, Canada

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Brampton, Ontario, Canada

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Oshawa, Ontario, Canada

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Rimouski, Quebec, Canada

Countries

United States; Canada

Other Identifiers

CLAP016A2306

Identifier Type: OTHER

Identifier Source: secondary_id

112515

Identifier Type: -

Identifier Source: org_study_id