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CancerPhase 3NCT00968968

Continued HER2 Suppression With Lapatinib Plus Trastuzumab Versus Trastuzumab Alone

A Phase 3 study testing Lapatinib and Trastuzumab in people with Cancer, run by Novartis Pharmaceuticals at 116 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Cancer
What is being tested?
Lapatinib and Trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
116 sitesin 2 countries
Study dates
20 Jan 2010to 30 Mar 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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]
Show all 15Show fewer
  • 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

Who cannot join

  • 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)
Show all 17Show fewer
  • 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

Trial locations and contacts

116 sites in 2 countries.

116 sites in 2 countries

United States112 sites

  • Novartis Investigative Site

    Abilene, Texas, 79606-5208

  • Novartis Investigative Site

    Abington, Pennsylvania, 19001

  • Novartis Investigative Site

    Arlington, Virginia, 22205

  • Novartis Investigative Site

    Arlington Heights, Illinois, 60005

  • Novartis Investigative Site

    Augusta, Georgia, 30901

  • Novartis Investigative Site

    Augusta, Georgia, 30909

  • Novartis Investigative Site

    Bakersfield, California, 93309

  • Novartis Investigative Site

    Beaumont, Texas, 77701

  • Novartis Investigative Site

    Bedford, Texas, 76022

  • Novartis Investigative Site

    Beverly Hills, California, 90211

  • Novartis Investigative Site

    Billings, Montana, 59102

  • Novartis Investigative Site

    Boston, Massachusetts, 02114

  • Novartis Investigative Site

    Boston, Massachusetts, 02215

  • Novartis Investigative Site

    Bountiful, Utah, 84010

  • Novartis Investigative Site

    Brownstown, Michigan, 48183

  • Novartis Investigative Site

    Burnsville, Minnesota, 55337

  • Novartis Investigative Site

    Cary, North Carolina, 27518

  • Novartis Investigative Site

    Chandler, Arizona, 85224

  • Novartis Investigative Site

    Chesapeake, Virginia, 23320

  • Novartis Investigative Site

    Chicago, Illinois, 60611

  • Novartis Investigative Site

    Columbia, Maryland, 21044

  • Novartis Investigative Site

    Columbia, Missouri, 65201

  • Novartis Investigative Site

    Coon Rapids, Minnesota, 55433

  • Novartis Investigative Site

    Dallas, Texas, 75230

  • Novartis Investigative Site

    Dearborn, Michigan, 48126

  • Novartis Investigative Site

    Detroit, Michigan, 48202

  • Novartis Investigative Site

    Dublin, Georgia, 31021

  • Novartis Investigative Site

    Edina, Minnesota, 55435

  • Novartis Investigative Site

    Edmonds, Washington, 98026

  • Novartis Investigative Site

    El Paso, Texas, 79902

  • Novartis Investigative Site

    El Paso, Texas, 79915

  • Novartis Investigative Site

    Elizabeth City, North Carolina, 27909

  • Novartis Investigative Site

    Evanston, Illinois, 60201

  • Novartis Investigative Site

    Fairfax, Virginia, 22031

  • Novartis Investigative Site

    Federal Way, Washington, 98003

  • Novartis Investigative Site

    Flagstaff, Arizona, 86001

  • Novartis Investigative Site

    Fort Worth, Texas, 76104

  • Novartis Investigative Site

    Fort Worth, Texas, 76132

  • Novartis Investigative Site

    Fridley, Minnesota, 55432

  • Novartis Investigative Site

    Fullerton, California, 92835

  • Novartis Investigative Site

    Gainesville, Virginia, 20155

  • Novartis Investigative Site

    Garland, Texas, 75042

  • Novartis Investigative Site

    Gig Harbor, Washington, 98332

  • Novartis Investigative Site

    Gilbert, Arizona, 85297

  • Novartis Investigative Site

    Glenview, Illinois, 60025

  • Novartis Investigative Site

    Goshen, Indiana, 46526

  • Novartis Investigative Site

    Grapevine, Texas, 76051

  • Novartis Investigative Site

    Greensboro, North Carolina, 27403

  • Novartis Investigative Site

    Hampton, Virginia, 23666

  • Novartis Investigative Site

    Henderson, Nevada, 89052

  • Novartis Investigative Site

    Henderson, Nevada, 89074

  • Novartis Investigative Site

    Highland Park, Illinois, 60035

  • Novartis Investigative Site

    Hollywood, Florida, 33021

  • Novartis Investigative Site

    Houston, Texas, 77024

  • Novartis Investigative Site

    Hudson, Florida, 34667

  • Novartis Investigative Site

    Jefferson City, Missouri, 65109

  • Novartis Investigative Site

    Joliet, Illinois, 60435

  • Novartis Investigative Site

    Kerrville, Texas, 78028

  • Novartis Investigative Site

    La Jolla, California, 92037

  • Novartis Investigative Site

    La Jolla, California, 92093-0987

  • Novartis Investigative Site

    Lakewood, Washington, 98499

  • Novartis Investigative Site

    Las Vegas, Nevada, 89128

  • Novartis Investigative Site

    Las Vegas, Nevada, 89148

  • Novartis Investigative Site

    Las Vegas, Nevada, 89169

  • Novartis Investigative Site

    Layton, Utah, 84041

  • Novartis Investigative Site

    Leesburg, Virginia, 20176

  • Novartis Investigative Site

    Long Beach, California, 90813

  • Novartis Investigative Site

    Los Angeles, California, 90095- 7187

  • Novartis Investigative Site

    Maplewood, Minnesota, 55109

  • Novartis Investigative Site

    Mesa, Arizona, 85202

  • Novartis Investigative Site

    Mesa, Arizona, 85206

  • Novartis Investigative Site

    Minneapolis, Minnesota, 55404

  • Novartis Investigative Site

    Mishawaka, Indiana, 46545

  • Novartis Investigative Site

    Murray, Utah, 84157-7000

  • Novartis Investigative Site

    New Port Richey, Florida, 34655

  • Novartis Investigative Site

    Newport News, Virginia, 23606

  • Novartis Investigative Site

    Niles, Illinois, 60714

  • Novartis Investigative Site

    Norfolk, Virginia, 23502

  • Novartis Investigative Site

    Odessa, Texas, 79761

  • Novartis Investigative Site

    Peoria, Illinois, 61615

  • Novartis Investigative Site

    Peoria, Illinois, 61636

  • Novartis Investigative Site

    Peoria, Illinois, 61637

  • Novartis Investigative Site

    Philadelphia, Pennsylvania, 19106

  • Novartis Investigative Site

    Plano, Texas, 75075

  • Novartis Investigative Site

    Plano, Texas, 75093

  • Novartis Investigative Site

    Provo, Utah, 84604

  • Novartis Investigative Site

    Puyallup, Washington, 98372

  • Novartis Investigative Site

    Radnor, Pennsylvania, 19087

  • Novartis Investigative Site

    Raleigh, North Carolina, 27607

  • Novartis Investigative Site

    Raleigh, North Carolina, 27614

  • Novartis Investigative Site

    Saint Paul, Minnesota, 55102

  • Novartis Investigative Site

    Salt Lake City, Utah, 84102

  • Novartis Investigative Site

    Salt Lake City, Utah, 84106

  • Novartis Investigative Site

    San Antonio, Texas, 78217

  • Novartis Investigative Site

    San Antonio, Texas, 78258-3912

  • Novartis Investigative Site

    San Diego, California, 92103-8411

  • Novartis Investigative Site

    San Pablo, California, 94806

  • Novartis Investigative Site

    Sandy City, Utah, 84094

  • Novartis Investigative Site

    Santa Maria, California, 93454

  • Novartis Investigative Site

    Seattle, Washington, 98104

  • Novartis Investigative Site

    Seattle, Washington, 98133

  • Novartis Investigative Site

    Sedona, Arizona, 86336

  • Novartis Investigative Site

    Silver Spring, Maryland, 20910

  • Novartis Investigative Site

    Skokie, Illinois, 60076

  • Novartis Investigative Site

    Tacoma, Washington, 98405

  • Novartis Investigative Site

    Tucson, Arizona, 85724

  • Novartis Investigative Site

    Virginia Beach, Virginia, 23456

  • Novartis Investigative Site

    Washington, North Carolina, 27889

  • Novartis Investigative Site

    West Bloomfield, Michigan, 48322

  • Novartis Investigative Site

    Williamsburg, Virginia, 23185

  • Novartis Investigative Site

    Winfield, Illinois, 60190

  • Novartis Investigative Site

    Woodbury, Minnesota, 55125

Other trials in United States

Canada4 sites

  • Novartis Investigative Site

    Brampton, Ontario, L6R 3J7

  • Novartis Investigative Site

    Halifax, Nova Scotia, B3H 1V7

  • Novartis Investigative Site

    Oshawa, Ontario, L1G 2B9

  • Novartis Investigative Site

    Rimouski, Quebec, G5L 5T1

Other trials in Canada

About this study

Official title: A Randomized, Phase III, Open-label Study of Lapatinib Plus Trastuzumab Versus Trastuzumab as Continued HER2 Suppression Therapy After Completion of First- or Second-line Trastuzumab Plus Chemotherapy in Subjects With HER2-positive Metastatic Breast Cancer

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
Being tested
Lapatinib, Trastuzumab
Keywords
carcinoma, breast lump, Pagets disease, breast cancer positive for human epidermal growth factor receptor 2, breast cancer progression, estrogen-receptor
Medical subject headings
Neoplasms, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LapatinibDrug

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

  • TrastuzumabBiological

    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.

Study groups in NCT00968968
Study groupRoleWhat they receive
Arm 1: Lapatinib plus TrastuzumabExperimentalNot described
Receives: Drug: Lapatinib; Biological: Trastuzumab
Arm 2: TrastuzumabActive comparatorNot described
Receives: Biological: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Overall Survival

    Overall Survival is defined as the interval of time (in months) between the date of randomization and the date of death due to any cause.

    Measured: Time from randomization until death, approximately 4 years

  2. Best Overall Response

    The best overall response was the best response from the start of the treatment until disease progression/recurrence and was determined programmatically using investigators assessment of responses of target lesion, non-target lesion and new lesions based on RECIST v1.1. Complete Response (CR) = disappearance of all target lesion and non-target lesions if applicable, and no new lesion; Partial Response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions and non-target lesion was neither complete response nor progressive disease (Non-CR/Non-PD) or not evaluable (NE); SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD = ≥ 20% increase from nadir of the target lesions or appearance of new lesion. CR and PR were confirmed responses. Confirmed CR - at least two determinations of CR at least 4 weeks apart before PD; Confirmed PR - at least two determinations of PR or better at least 4 weeks apart before PD.

    Measured: approximately 4 years

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

    Clinical Benefit Rate (CBR) was defined as the percentage of patients achieving either a confirmed CR or PR at any time or maintaining SD for at least 24 weeks while on study, according to the investigator assessment of response per RECIST 1.1 criteria.

    Confirmed CR - at least two determinations of CR at least 4 weeks apart before PD; Confirmed PR - at least two determinations of PR or better at least 4 weeks apart before PD.

    Measured: approximately 4 years

  4. Adverse Event Profile of the Two Treatment Arms

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2009 (estimated)
  2. Study start20 Jan 2010
  3. Primary completion21 Feb 2014
  4. Study completion30 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00968968
Sponsor's protocol ID
112515
Other IDs
CLAP016A2306
Status last verified
Jun 2019
First submitted
27 Aug 2009
Last updated
10 Jun 2019
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lapatinib and Trastuzumab in people with Cancer, run by Novartis Pharmaceuticals at 116 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 116 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: Time from randomization until disease progression or death, approximately 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00968968.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019.

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