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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

January 23, 2006
January 16, 2014
April 2004
June 2010   (final data collection date for primary outcome measure)
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.
Clinical benefit: evaluation of tumors for progression/response
Complete list of historical versions of study NCT00281658 on ClinicalTrials.gov Archive Site
  • 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.
Safety Overall survival Time to response Duration of response
Not Provided
Not Provided
 
Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Neoplasms, Breast
  • Drug: lapatinib (GW572016) oral tablets
    1500 mg oral daily continuously
  • 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
  • Experimental: Combination
    Paclitaxel and Lapatinib (Blinded)
    Intervention: Drug: paclitaxel infusion
  • Active Comparator: Paclitaxel
    Paclitaxel and Placebo (Blinded)
    Intervention: Drug: paclitaxel infusion
  • Monotherapy Extension
    Open-label monotherapy lapatinib
    Intervention: Drug: lapatinib (GW572016) oral tablets

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
444
June 2014
June 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Brazil,   China,   Hong Kong,   Pakistan,   Peru,   Russian Federation,   Thailand,   Ukraine
 
NCT00281658
EGF104535
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP