Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer

NCT00470704 | Completed Phase 2 Results DMC

• 1 other identifier: 06-213
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 9

Brief Summary

In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.

Conditions

Breast Cancer

Keywords

HER2-positive breast cancer; Herceptin; trastuzumab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The objective response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.

  8 weeks

Secondary Outcomes (5)

• Top 3 Most Common Treatment RelatedToxicities

  Up to 93 months

• Sites of First Progression

  Up to 93 months

• Clinical Benefit Rate

  Up to 93 months

• 3-Year Overall Survival

  Up to 93 months

• Median Time to Progression

  Up to 93 months

Study Arms (2)

Cohort 1

OTHER

This cohort is made up of participants without prior trastuzumab for MBC. Adjuvant or neoadjuvant trastuzumab was allowed, if the interval from trastuzumab completion to recurrence exceeded 1 year. 1000 mg daily Lapatinib 2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab

Drug: Lapatinib; Drug: Herceptin

Cohort 2

OTHER

This cohort is made up of participants with one to two lines of chemotherapy for metastatic disease with at least one trastuzumab-containing regimen or patients who recurred within 12 months of adjuvant or neoadjuvant trastuzumab with up to one line of metastatic trastuzumab-based therapy 1000 mg daily Lapatinib 2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab

Drug: Lapatinib; Drug: Herceptin

Interventions

Lapatinib DRUG

Also known as: Tykerb

Cohort 1; Cohort 2

Herceptin DRUG

Also known as: trastuzumab

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
• HER2-positive breast cancer, defined as 3+ staining by IHC or gene amplification by FISH
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
• Willingness to undergo a research biopsy of recurrent or metastatic disease
• Prior chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry.
• Completed radiation therapy at least 7 days prior to beginning protocol treatment
• Cohort 1: No prior chemotherapy for advanced breast cancer; no prior trastuzumab in the advanced breast cancer setting; nor prior treatment with lapatinib or other HER2-directed therapy other than trastuzumab
• Cohort 2: Up to two prior chemotherapy regimens for the treatment of advanced breast cancer; no prior treatment with lapatinib or other HER2-directed therapy except for trastuzumab
• years of age or older
• Life expectancy of greater than 12 weeks
• ECOG Performance Status 0-2
• Normal organ and marrow function as outlined in protocol
• Cardiac ejection fraction, as assessed by either MUGA scan or echocardiogram greater than or equal to 50%
• Able to take oral medications

You may not qualify if:

• Patients may not be receiving any other investigational agents or concurrent chemotherapy or hormonal therapy for treatment of metastatic disease
• Active brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in this study
• Clinically significant malabsorption syndrome
• Uncontrolled intercurrent illness
• Pregnant or breastfeeding women
• Concurrent use of the medications listed in the protocol because of possible interaction with lapatinib

Sponsors & Collaborators

• Nancy Lin, MD: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (9)

University fo Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Chicago

Chicago, Illinois, 60452, United States

Location

Dana-Farber at Faulkner Hospital

Boston, Massachusetts, 02130, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lin NU, Guo H, Yap JT, Mayer IA, Falkson CI, Hobday TJ, Dees EC, Richardson AL, Nanda R, Rimawi MF, Ryabin N, Najita JS, Barry WT, Arteaga CL, Wolff AC, Krop IE, Winer EP, Van den Abbeele AD. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003). J Clin Oncol. 2015 Aug 20;33(24):2623-31. doi: 10.1200/JCO.2014.60.0353. Epub 2015 Jul 13.

  PMID: 26169615 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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

Results Point of Contact

• Title: Nancy Lin
• Organization: Dana-Farber Cancer Institute

Nancy_Lin@dfci.harvard.edu

6176322335

Study Officials

• Nancy Lin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 7, 2007
• First Posted: May 8, 2007
• Study Start: May 14, 2007
• Primary Completion: November 30, 2013
• Study Completion: August 20, 2024
• Last Updated: December 19, 2024
• Results First Posted: March 15, 2022

Record last verified: 2024-12

Locations

US (9)