Continued HER2 Suppression With Lapatinib Plus Trastuzumab Versus Trastuzumab Alone

NCT00968968 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: 112515CLAP016A2306
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 116

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

Keywords

carcinoma, breast lump, Pagets disease, breast cancer positive for human epidermal growth factor receptor 2, breast cancer progression, estrogen-receptor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival (PFS) with lapatinib plus trastuzumab versus trastuzumab alone. Progression-free survival (PFS) is defined as the time from randomization to the earliest date of disease progression (with radiological evidence) or death from any cause, or to last contact date up to 21Feb2014. Disease Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1), a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum diameters recorded since the treatment started (the sum must have an absolute increase from nadir of 5mm), or an unequivocal progression of existing non-target lesions, or the appearance of new lesions.

  Time from randomization until disease progression or death, approximately 4 years

Secondary Outcomes (4)

• Overall Survival

  Time from randomization until death, approximately 4 years

• Best Overall Response

  approximately 4 years

• Clinical Benefit Response Rate (CR, PR or SD ≥24 Weeks)

  approximately 4 years

• Adverse Event Profile of the Two Treatment Arms

  From first dose of study treatment until 30 days after the last dose of study treatment, approximately 8 years.

Study Arms (2)

Arm 1: Lapatinib plus Trastuzumab

EXPERIMENTAL

Drug: Lapatinib; Biological: Trastuzumab

Arm 2: Trastuzumab

ACTIVE COMPARATOR

Biological: Trastuzumab

Interventions

Lapatinib DRUG

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

Arm 1: Lapatinib plus Trastuzumab

Trastuzumab 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 1: Lapatinib plus Trastuzumab; Arm 2: Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• + 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (116)

Novartis Investigative Site

Chandler, Arizona, 85224, United States

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Flagstaff, Arizona, 86001, United States

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Gilbert, Arizona, 85297, United States

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Mesa, Arizona, 85202, United States

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Mesa, Arizona, 85206, United States

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Sedona, Arizona, 86336, United States

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Tucson, Arizona, 85724, United States

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Bakersfield, California, 93309, United States

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Beverly Hills, California, 90211, United States

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Fullerton, California, 92835, United States

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La Jolla, California, 92037, United States

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La Jolla, California, 92093-0987, United States

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Long Beach, California, 90813, United States

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Los Angeles, California, 90095- 7187, United States

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San Diego, California, 92103-8411, United States

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San Pablo, California, 94806, United States

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Santa Maria, California, 93454, United States

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Hollywood, Florida, 33021, United States

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Hudson, Florida, 34667, United States

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New Port Richey, Florida, 34655, United States

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Augusta, Georgia, 30901, United States

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Augusta, Georgia, 30909, United States

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Dublin, Georgia, 31021, United States

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Arlington Heights, Illinois, 60005, United States

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Chicago, Illinois, 60611, United States

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Evanston, Illinois, 60201, United States

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Glenview, Illinois, 60025, United States

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Highland Park, Illinois, 60035, United States

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Joliet, Illinois, 60435, United States

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Niles, Illinois, 60714, United States

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Peoria, Illinois, 61615, United States

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Peoria, Illinois, 61636, United States

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Peoria, Illinois, 61637, United States

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Skokie, Illinois, 60076, United States

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Winfield, Illinois, 60190, United States

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Goshen, Indiana, 46526, United States

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Mishawaka, Indiana, 46545, United States

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Columbia, Maryland, 21044, United States

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Silver Spring, Maryland, 20910, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Brownstown, Michigan, 48183, United States

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Dearborn, Michigan, 48126, United States

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Detroit, Michigan, 48202, United States

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West Bloomfield, Michigan, 48322, United States

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Burnsville, Minnesota, 55337, United States

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Coon Rapids, Minnesota, 55433, United States

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Edina, Minnesota, 55435, United States

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Fridley, Minnesota, 55432, United States

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Maplewood, Minnesota, 55109, United States

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Minneapolis, Minnesota, 55404, United States

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Saint Paul, Minnesota, 55102, United States

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Woodbury, Minnesota, 55125, United States

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Columbia, Missouri, 65201, United States

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Jefferson City, Missouri, 65109, United States

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Billings, Montana, 59102, United States

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Henderson, Nevada, 89052, United States

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Henderson, Nevada, 89074, United States

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Las Vegas, Nevada, 89128, United States

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Las Vegas, Nevada, 89148, United States

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Las Vegas, Nevada, 89169, United States

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Cary, North Carolina, 27518, United States

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Elizabeth City, North Carolina, 27909, United States

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Greensboro, North Carolina, 27403, United States

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Raleigh, North Carolina, 27607, United States

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Raleigh, North Carolina, 27614, United States

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Washington, North Carolina, 27889, United States

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Abington, Pennsylvania, 19001, United States

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Philadelphia, Pennsylvania, 19106, United States

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Radnor, Pennsylvania, 19087, United States

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Abilene, Texas, 79606-5208, United States

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Beaumont, Texas, 77701, United States

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Bedford, Texas, 76022, United States

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Dallas, Texas, 75230, United States

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El Paso, Texas, 79902, United States

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El Paso, Texas, 79915, United States

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Fort Worth, Texas, 76104, United States

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Fort Worth, Texas, 76132, United States

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Garland, Texas, 75042, United States

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Grapevine, Texas, 76051, United States

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Houston, Texas, 77024, United States

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Kerrville, Texas, 78028, United States

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Odessa, Texas, 79761, United States

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Plano, Texas, 75075, United States

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Plano, Texas, 75093, United States

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San Antonio, Texas, 78217, United States

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San Antonio, Texas, 78258-3912, United States

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Bountiful, Utah, 84010, United States

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Layton, Utah, 84041, United States

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Murray, Utah, 84157-7000, United States

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Provo, Utah, 84604, United States

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Salt Lake City, Utah, 84102, United States

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Salt Lake City, Utah, 84106, United States

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Sandy City, Utah, 84094, United States

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Arlington, Virginia, 22205, United States

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Chesapeake, Virginia, 23320, United States

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Fairfax, Virginia, 22031, United States

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Gainesville, Virginia, 20155, United States

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Hampton, Virginia, 23666, United States

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Leesburg, Virginia, 20176, United States

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Newport News, Virginia, 23606, United States

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Norfolk, Virginia, 23502, United States

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Virginia Beach, Virginia, 23456, United States

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Williamsburg, Virginia, 23185, United States

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Edmonds, Washington, 98026, United States

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Federal Way, Washington, 98003, United States

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Gig Harbor, Washington, 98332, United States

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Lakewood, Washington, 98499, United States

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Puyallup, Washington, 98372, United States

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Seattle, Washington, 98104, United States

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Seattle, Washington, 98133, United States

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Tacoma, Washington, 98405, United States

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Halifax, Nova Scotia, B3H 1V7, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Rimouski, Quebec, G5L 5T1, Canada

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MeSH Terms

Conditions

Neoplasms; Carcinoma

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

This study was closed to further enrollment since the enrollment rate would not allow the study to complete enrollment within an acceptable timeframe.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2009
• First Posted: August 31, 2009
• Study Start: January 20, 2010
• Primary Completion: February 21, 2014
• Study Completion: March 30, 2018
• Last Updated: June 10, 2019
• Results First Posted: June 10, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

US (112); CA (4)