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Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00281658
First received: January 23, 2006
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

This is a Phase III study designed to evaluate the response (shrinkage or lack of growth) of tumors of lapatinib plus paclitaxel compared to paclitaxel plus placebo as first line metastatic treatment in women and men who have metastatic breast cancer. Patients will be evaluated for safety and efficacy. Countries include China, Hong Kong, Thailand, Brazil and Peru.


Condition Intervention Phase
Neoplasms, Breast
Drug: lapatinib (GW572016) oral tablets
Drug: paclitaxel infusion
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study of Lapatinib (GW572016) in Combination With Paclitaxel Versus Paclitaxel Plus Placebo in Subjects With ErbB2 Amplified Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Randomization to death (up to maximum of Month 53) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization until death due to any cause.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from randomization until the earliest date of disease progression (radiological or clinical assessment of symptomatic progression) or death due to any cause, if sooner during the randomized phase. Disease progression is based on the assessments by the investigator.

  • Overall Response (OR) [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ] [ Designated as safety issue: No ]
    OR, evaluated per Response Evaluation Criteria in Solid Tumors (RECIST), is defined as the number of participants achieving either a confirmed complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) of tumor, which were based on confirmed responses from the investigator assessment of best OR during the randomized phase. Participants with unknown or missing responses were treated as non-responders.

  • Clinical Benefit [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ] [ Designated as safety issue: No ]
    Clinical benefit is defined as the number of participants achieving either a confirmed CR or PR or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesions], taking as reference the smallest sum LD since treatment start) of >=24 weeks, based on confirmed responses from the investigator assessment of best overall response during the randomized phase.

  • Duration of Response [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ] [ Designated as safety issue: No ]
    Duration of response is defined for the subset of participants with a confirmed CR or PR as the time from first documented evidence of CR or PR until the first documented sign of disease progression (radiological or clinical assessment of symptomatic progression) or death due to any cause during the randomized phase. Only participants with a confirmed CR or PR were included in this analysis. Disease progression is based on the assessments by the investigator.

  • Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 [ Time Frame: Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 ] [ Designated as safety issue: No ]
    The original outcome measure to be analyzed was time to response; however, data are presented as the number of participants with a response at each nominal visit. Responses are based on the investigator's assessment, and only participants with a confirmed CR or PR were included in this analysis.


Enrollment: 444
Study Start Date: April 2004
Estimated Study Completion Date: June 2014
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination
Paclitaxel and Lapatinib (Blinded)
Drug: paclitaxel infusion
Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months
Other Names:
  • paclitaxel infusion
  • lapatinib (GW572016) oral tablets
Active Comparator: Paclitaxel
Paclitaxel and Placebo (Blinded)
Drug: paclitaxel infusion
Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months
Other Names:
  • paclitaxel infusion
  • lapatinib (GW572016) oral tablets
Monotherapy Extension
Open-label monotherapy lapatinib
Drug: lapatinib (GW572016) oral tablets
1500 mg oral daily continuously

Detailed Description:

Patients must with Her2+(ErbB2+) MBC Stage IV, newly diagnosed will receive paclitaxel+lapatinib or paclitaxel plus placebo for 6 cycles minimum. After 6 cycles continue to receive blinded monotherapy until progression. Safety evaluations include evaluating adverse events, hematology/ chemistry tests, vital signs, and cardiac muga scans. Efficacy assessments include evaluation of disease per RECIST. All patients followed for overall survival (OS).

Study conducted in regions were access to trastuzumab is limited.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Signed informed consent;
  • Male or female ≥18 years;
  • Histologically confirmed invasive breast cancer with stage IV disease; If the disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.
  • Documented amplification of ErbB2 by fluorescence in situ hybridization (FISH) in primary or metastatic tumor tissue by the central laboratory for randomization into the study;
  • If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred >12 months after completion of this treatment and the patient recovered from all associated toxicities;
  • Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors);
  • Radiotherapy as palliative treatment for painful metastatic disease is permitted but must have been stopped within 2 weeks prior to initiation of any investigational treatment. All subjects must have recovered from all radiotherapy related toxicities prior to initiation of any investigational treatment. The site of radiotherapy must not be used as a site of measurable disease;
  • Bisphosphonate therapy for bone metastases and is allowed; however, treatment must be initiated prior to the first dose of investigational treatment. Prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for the treatment of osteoporosis;
  • For those patients whose disease is ER+ and/or PR+ the following criteria should be met:

Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) Rapidly progressing or life threatening disease, as determined by the investigator Patients who received hormonal therapy and are no longer benefiting from this therapy and the hormonal treatment must have been stopped before the first dose of investigational treatment;

  • Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive;
  • ECOG Performance Status of 0 to 1;
  • Life expectancy of ≥ 12 weeks;
  • Able to swallow and retain oral medication;
  • Archived tumor tissue available for testing;
  • Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study;
  • Willing to complete all screening assessments as outlined in the protocol;
  • Adequate organ function as defined in Table 1 Baseline Laboratory Values;

Exclusion Criteria:

  • Pregnant or lactating females at anytime during the study
  • Subjects with only non-measurable metastatic sites of disease per RECIST, (e.g. bone metastases, pleural effusion, or ascites, etc. (Refer to Section 5.3 Efficacy for list sites considered to be non-measurable disease.);
  • Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease.
  • Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab in the adjuvant setting. If trastuzumab was administered in the adjuvant setting, then > 12 months must have elapsed since completion of trastuzumab therapy;
  • Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment;
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
  • Peripheral neuropathy of Grade 2 or greater;
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
  • History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible;
  • Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety;
  • Uncontrolled infection;
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
  • Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
  • Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
  • Concurrent treatment with prohibited medications, including herbal remedies and Chinese traditional medicines;
  • Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents;
  • Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of investigational treatment;
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel or lapatinib or their excipients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281658

  Hide Study Locations
Locations
Brazil
GSK Investigational Site
Salvador, Bahía, Brazil, 40.050-410
GSK Investigational Site
Salvador, Bahía, Brazil, 40285-001
GSK Investigational Site
Belo Horizonte, Minas Gerais, Brazil, 30150-281
GSK Investigational Site
Porto Alegre, Rio Grande Do Sul, Brazil, 90610 000
GSK Investigational Site
Natal, Rio Grande Du Norte, Brazil, 59075-740
GSK Investigational Site
Jaú, São Paulo, Brazil, 17210-120
GSK Investigational Site
Santo André, São Paulo, Brazil, 09060-650
GSK Investigational Site
São Paulo, Brazil, 03102-002
GSK Investigational Site
São Paulo, Brazil, 01221-020
China, Guangdong
GSK Investigational Site
Guangzhou, Guangdong, China, 510060
China, Hubei
GSK Investigational Site
Wuhan, Hubei, China, 430030
China, Jiangsu
GSK Investigational Site
Nanjing, Jiangsu, China, 210002
GSK Investigational Site
Nanjing, Jiangsu, China, 210009
China, Liaoning
GSK Investigational Site
Dalian, Liaoning, China, 116027
China, Shaanxi
GSK Investigational Site
Xi'an, Shaanxi, China, 710032
GSK Investigational Site
Xi'an, Shaanxi, China, 710061
China, Shandong
GSK Investigational Site
Jinan, Shandong, China, 250012
GSK Investigational Site
Jinan, Shandong, China, 250117
GSK Investigational Site
Jinan, Shandong, China, 250031
China, Zhejiang
GSK Investigational Site
Hangzhou, Zhejiang, China, 310022
China
GSK Investigational Site
Beijing, China, 100071
GSK Investigational Site
Beijing, China, 100853
GSK Investigational Site
Beijing, China, 100021
GSK Investigational Site
Beijing, China, 100036
GSK Investigational Site
Chengdu, China, 610041
GSK Investigational Site
Chongqing, China, 400037
GSK Investigational Site
Dalian, China, 116011
GSK Investigational Site
Fuzhou, China, 350001
GSK Investigational Site
Fuzhou, China, 350014
GSK Investigational Site
Shanghai, China, 200070
GSK Investigational Site
Shanghai, China, 200032
GSK Investigational Site
Shanghai, China, 200433
GSK Investigational Site
Shenyang, China, 110015
GSK Investigational Site
Tianjin, China, 300060
Hong Kong
GSK Investigational Site
Kowloon, Hong Kong
GSK Investigational Site
Pokfulam, Hong Kong
GSK Investigational Site
Tuen Mun, Hong Kong
Pakistan
GSK Investigational Site
Lahore, Pakistan
GSK Investigational Site
Lahore, Pakistan, 54600
GSK Investigational Site
Lahore, Pakistan, 53400
Peru
GSK Investigational Site
Lima, Peru, Lima 34
Russian Federation
GSK Investigational Site
Kazan, Russian Federation, 420029
GSK Investigational Site
Moscow, Russian Federation, 143423
GSK Investigational Site
Moscow, Russian Federation, 125101
GSK Investigational Site
Moscow, Russian Federation, 117997
GSK Investigational Site
Rostov-na-Donu, Russian Federation, 344037
GSK Investigational Site
Samara, Russian Federation, 443031
GSK Investigational Site
Voronezh, Russian Federation, 394062
Thailand
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Chiangmai, Thailand, 50200
Ukraine
GSK Investigational Site
Cherkasy, Ukraine, 18009
GSK Investigational Site
Chernihiv, Ukraine, 14029
GSK Investigational Site
Dnipropetrovsk, Ukraine, 49055
GSK Investigational Site
Zaporizhzhia, Ukraine, 69040
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00281658     History of Changes
Other Study ID Numbers: EGF104535
Study First Received: January 23, 2006
Results First Received: May 5, 2011
Last Updated: January 16, 2014
Health Authority: Ukraine: Central Ethics Committee;
Brazil: Institutional Review Board
Peru: Institutional Review Board
Norway: Statens Legemiddelverk
Russia: Russian Ministry of Health
Thailand: Ministry of Public Health
Hong Kong: Department of Health
China: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
ErbB2 positive
Her2+
metastatic breast cancer
FISH positive
Stage IV

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Lapatinib
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 23, 2014