Overview

This trial is active, not recruiting.

Condition neoplasms, breast
Treatments lapatinib, paclitaxel, trastuzumab
Phase phase 3
Targets HER2, AKT, CDK, EGFR, ERK
Sponsor GlaxoSmithKline
Start date December 2005
End date July 2009
Trial size 63 participants
Trial identifier NCT00272987, EGF104383

Summary

Patients will be randomised to a 1:1 ratio to receive either paclitaxel 80 mg/m2 IV weekly for three weeks of a four week cycle, trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly IV, and oral lapatinib 1000 mg QD or paclitaxel 80 mg/m2 IV weekly for three weeks of a four week cycle, trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly IV plus placebo. The primary objective of this study is to evaluate and compare time to progression (TTP). Secondary objectives will be to evaluate and compare the two treatment arms with respect to: overall response rates, clinical benefit, time to response, duration of response, progression-free survival, and overall survival. The study will first enroll an open label safety cohort of 20 patients to assess the tolerability of the triplet combination.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Open label safety phase. All patients received paclitaxel + trastuzumab + lapatinib.
lapatinib
(GW572016) 1000 mg QD
paclitaxel
80 mg/m2 IV weekly for three weeks
trastuzumab
4 mg/kg loading dose and 2 mg/kg weekly IV

Primary Outcomes

Measure
Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel
time frame: From the date of the first dose of the investigational product up to withdrawal/study completion (up to Study Week 164)
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to Study Week 164)
Number of Participants Who Died Due to Any Cause
time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to Study Week 164)
Number of Events of Diarrhea With the Indicated Characteristics
time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to Study Week 164)
Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters
time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters
time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Number of Events of Hepatotoxicity With the Indicated Characteristics
time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to Study Week 164)
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points
time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Change From Baseline in Heart Rate at the Indicated Time Points
time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Change From Baseline in Body Temperature at the Indicated Time Points
time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Number of Events of Left Ventricular Ejection Fraction Decrease With the Indicated Characteristics
time frame: Baseline and every 8 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value
time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up (up to Study Week 164)
Number of Participants Who Received Any Concomitant Medications During the Study Period
time frame: withdrawal/study completion (up to Study Week 164)
Overall Response (OR): Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator
time frame: From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 164)

Secondary Outcomes

Measure
Time to Response as Assessed by the Investigator
time frame: From the date of the first dose of investigational product until the first documented evidence of a PR or CR (up to Study Week 164)
Duration of Response (DoR), as Assessed by the Investigator
time frame: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Study Week 164)
Number of Participants With Clinical Benefit (CR, PR, and Stable Disease [SD] for at Least 24 Weeks) as Assessed by Investigator
time frame: From the date of the first dose of investigational product until the first documented evidence of a PR or CR or SD until the earlier of the date of disease progression or the date of death due to breast cancer (up to Study Week 164)
Progression-free Survival as Assessed by the Investigator
time frame: From the date of the first dose of investigational product until the earlier of the date of disease progression or death due to any cause (up to Study Week 164)

Eligibility Criteria

Female participants at least 18 years old.

Inclusion criteria: - Histologically confirmed invasive breast cancer with stage IV disease If trastuzumab was administered in the adjuvant setting, >12 months must have elapsed since discontinuation of trastuzumab therapy - If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred 12 months after completion of this treatment - Had tumors that overexpress ErbB2 (Immunohistochemistry 3+ or Fluorescent in-situ hybridisation gene amplification) - Patients must have tumor tissue available for central testing Measurable lesion(s) - Subjects must be females of at least 18 years Non-childbearing potential or Childbearing potential but using adequate contraception - Radiotherapy to a limited area other than the sole site of measurable and assessable disease is allowed; however, patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of study medication - Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 - For those patients whose disease is estrogen receptor positive+ and/or progesterone receptor + one the following criteria should be met: Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly progressing/life threatening disease, as determined by the investigator or Patients who received hormonal therapy and are no longer benefiting from this therapy; - Able to swallow and retain oral medication - Cardiac ejection fraction within institutional range of normal - Patient must have adequate organ function Exclusion criteria: - Pregnant or lactating females; - Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization; Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. - Patients with ulcerative colitis are also excluded; - History of other malignancy; however, patients who have been disease-free for five years, or patients 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 patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety; - 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; - Active or 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, conduction abnormalities or congestive heart failure; - Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis; - Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy); Concurrent treatment with an investigational agent or participation in another clinical trial; - Concurrent treatment with any medication on the prohibited medications list. - Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment. Hormonal therapy needs to be discontinued at least 7 days before the first dose of treatment. - Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting; - A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients; - A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients; - A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients; - Non compliance with any of the screening procedures

Additional Information

Official title A Randomized, Double Blind, Placebo-Controlled, Multicenter, Phase III Study Comparing the Activity of Paclitaxel Plus Trastuzumab Plus Lapatinib to Paclitaxel Plus Trastuzumab Plus Placebo in Women With ErbB2 Overexpressing Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.