Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer

NCT00263588 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: EGF105084CLAP016A22022005-003944-68
• Study Type: interventional
• Target: 242
• Locations: 16 countries
• Sites: 67

Brief Summary

Determine how safe and effective lapatinib is when used to treat patients with ErbB2 overexpressing breast cancer that has spread to the brain and is still progressing there even after radiation treatment using WBRT (whole brain radiotherapy) or SRS (stereotactic radiosurgery) to the brain. Lapatinib is an oral drug that will be taken every day. Tests for safety and efficacy will be performed every 4 weeks or 8 weeks (depending on the test) during the course of the study.

Conditions

Neoplasms, Breast

Keywords

breast cancer; brain metastases; ErbB2 positive; HER2 positive; neoplasms; cancer; lapatinib; LAP016A2202; LAP016A; CLAP016A2202; GW572016

Outcome Measures

Primary Outcomes (2)

• The Number of Participants With Central Nervous System (CNS) Best Overall Response

  Summary of CNS Objective Response (Lapatinib Monotherapy - MITT Population) Response to lapatinib in patients with progressive brain metastases from ErbB2-overexpressing breast cancer. The primary indicator of drug efficacy was CNS objective response rate. A CNS objective response was defined as either a Complete response (CR) or Partial response (PR), as assessed by volumetric analysis of brain Magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of Neurological signs and symptoms (NSS) A CNS objective response rate was defined as a 50% volumetric reduction in sum of CNS target lesions, with no new or progressive CNS or non-CNS lesions, no increases in tumor-related steroid requirements and no worsening of neurological signs or symptoms

  time from baseline to data cutoff (25 Sept 2007); approximately 2 years

• The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)

  Summary of CNS Objective Response (the Complete Response + Partial Response)

  time from baseline to data cutoff (25 Sept 2007); approximately 2 years

Secondary Outcomes (8)

• Percentage of Participants With Improvement in Neurological Signs and Symptoms (NSS) Measured Using the Neurological Examination Worksheet

  time from baseline to data cutoff (25 Sept 2007); approximately 2 years

• Percentage of Subjects With a CNS Objective Response or Improvement in Baseline Neurological Signs and Symptoms (NSS)

  baseline and weeks 8, 16, 24, 32, 40, 48

• Duration of Central Nervous System (CNS) Objective Response

  time from baseline to data cutoff (25 Sept 2007); approximately 2 years

• Percentage of Patients With CNS Disease Control (Complete Response, Partial Response or Stable Disease) at 6 Months of Lapatinib Therapy

  from Start of lapatinib to 6 months

• Time to Progression (TTP) at Any Site

  time from baseline to data cutoff (25 Sept 2007); approximately 2 years

Study Arms (1)

single arm

EXPERIMENTAL

750 mg lapatinib administered orally twice daily

Drug: lapatinib

Interventions

lapatinib DRUG

tyrosine kinase inhibitor

single arm

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent
• ErbB2(HER2)overexpressing breast cancer.
• Brain lesion(s) which are progressing.
• Prior treatment of brain metastases with Whole Brain Radiotherapy (WBR)and/or Stereotactic Radiosurgery (SRS).
• Prior treatment with trastuzumab (Herceptin), either alone or in combination with chemotherapy.
• Cardiac ejection fraction(LVEF)within the institutional range of normal as measured by Echocardiogram.
• Able to swallow an oral medication.
• Adequate kidney and liver function.
• Adequate bone marrow function.

You may not qualify if:

• Pregnant or lactating females.
• Conditions that would effect the absorption of an oral drug.
• History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents.
• Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel.
• Serious medical or psychiatric disorder that would interfere with the patient's safety or informed consent.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (74)

Novartis Investigative Site

San Francisco, California, 94115, United States

Location

Novartis Investigative Site

Vallejo, California, 94589, United States

Location

Novartis Investigative Site

Denver, Colorado, 80220, United States

Location

Novartis Investigative Site

Washington D.C., District of Columbia, 20007, United States

Location

Novartis Investigative Site

Boca Raton, Florida, 33428, United States

Location

Novartis Investigative Site

Jacksonville, Florida, 32224, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46202, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46227, United States

Location

Novartis Investigative Site

Sioux City, Iowa, 51101-1733, United States

Location

Novartis Investigative Site

Kansas City, Kansas, 66160, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109, United States

Location

Novartis Investigative Site

Minneapolis, Minnesota, 55455, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110-1093, United States

Location

Novartis Investigative Site

Albuquerque, New Mexico, 87106, United States

Location

Novartis Investigative Site

Albuquerque, New Mexico, 87108, United States

Location

Novartis Investigative Site

Albuquerque, New Mexico, 87131-0001, United States

Location

Novartis Investigative Site

Santa Fe, New Mexico, 87505, United States

Location

Novartis Investigative Site

New York, New York, 10021, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Novartis Investigative Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Dallas, Texas, 75246, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Tyler, Texas, 75702, United States

Location

Novartis Investigative Site

Seattle, Washington, 98109, United States

Location

Novartis Investigative Site

Yakima, Washington, 98902, United States

Location

Novartis Investigative Site

North Sydney, New South Wales, 2060, Australia

Location

Novartis Investigative Site

Herston, Queensland, 4029, Australia

Location

Novartis Investigative Site

South Brisbane, Queensland, 4101, Australia

Location

Novartis Investigative Site

Box Hill, Victoria, 3128, Australia

Location

Novartis Investigative Site

Ringwood East, Victoria, 3135, Australia

Location

Novartis Investigative Site

Perth, Western Australia, 6000, Australia

Location

Novartis Investigative Site

Adelaide, 5000, Australia

Location

Novartis Investigative Site

Salzburg, A-5020, Austria

Location

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1H 8L6, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5B 1W8, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Weston, Ontario, M9N 1N8, Canada

Location

Novartis Investigative Site

Dijon, 21079, France

Location

Novartis Investigative Site

Paris, 75010, France

Location

Novartis Investigative Site

Paris, 75248, France

Location

Novartis Investigative Site

Toulouse, 31052, France

Location

Novartis Investigative Site

Munich, Bavaria, 80637, Germany

Location

Novartis Investigative Site

Munich, Bavaria, 81377, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Neo Faliro, 18547, Greece

Location

Novartis Investigative Site

Bangalore, 560078, India

Location

Novartis Investigative Site

Mumbai, 400026, India

Location

Novartis Investigative Site

Reggio Emilia, Emilia-Romagna, 42100, Italy

Location

Novartis Investigative Site

Milan, Lombardy, 20141, Italy

Location

Novartis Investigative Site

Perugia, Umbria, 06156, Italy

Location

Novartis Investigative Site

Aichi, 464-8681, Japan

Location

Novartis Investigative Site

Saitama, 350-0495, Japan

Location

Novartis Investigative Site

Saitama, 350-1298, Japan

Location

Novartis Investigative Site

Tokyo, 104-0045, Japan

Location

Novartis Investigative Site

Tokyo, 113-8677, Japan

Location

Novartis Investigative Site

Tokyo, 135-8550, Japan

Location

Novartis Investigative Site

Olsztyn, 10-228, Poland

Location

Novartis Investigative Site

Warsaw, 02-781, Poland

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Uppsala, SE-751 85, Sweden

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Novartis Investigative Site

Locarno, 6600, Switzerland

Location

Novartis Investigative Site

Tainan County, 736, Taiwan

Location

Novartis Investigative Site

Taipei, 10016, Taiwan

Location

Novartis Investigative Site

Taipei, 114, Taiwan

Location

Novartis Investigative Site

Manchester, Lancashire, M20 4BX, United Kingdom

Location

Novartis Investigative Site

Brighton, BN2 5BE, United Kingdom

Location

Related Publications (1)

• Sutherland S, Ashley S, Miles D, Chan S, Wardley A, Davidson N, Bhatti R, Shehata M, Nouras H, Camburn T, Johnston SR. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases--the UK experience. Br J Cancer. 2010 Mar 16;102(6):995-1002. doi: 10.1038/sj.bjc.6605586. Epub 2010 Feb 23.

  PMID: 20179708 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Outcome Quantitative Toxicities Associated with Oral Lapatinib are in Adverse Events section. No analysis was performed for 2 outcomes: Relationship of PET Uptake, as Predictors of Response; and Relationship Between Genetic Variants in Select Genes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 (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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2005
• First Posted: December 9, 2005
• Study Start: December 2, 2005
• Primary Completion: September 25, 2007
• Study Completion: March 15, 2018
• Last Updated: December 12, 2019
• Results First Posted: December 12, 2019

Record last verified: 2019-11

Locations

PL (2); SE (1); AU (2); IT (3); IN (2); CH (2); GB (2); FR (4); CA (5); US (28); DE (3); JP (6); BE (1); GR (1); TW (3); ES (2)