An Open-label, Single-arm, Multi-centre, Phase II Study of Oral Lapatinib in Combination With Paclitaxel as First-line Treatment for ErbB2-amplified Metastatic Breast Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Lapatinib oral tablets
- Conditions
- Neoplasms, Breast
- Sponsor
- GlaxoSmithKline
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This study investigates the safety and efficacy of oral lapatinib in combination with an approved medication, paclitaxel, for patients with ErbB2 metastatic breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- •Signed informed consent.
- •Only females ≥18 years of age will be recruited:
- •Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
- •Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea (severe), women who are perimenopausal and young women who have begun to menstruate. These subjects must provide a negative serum pregnancy test at Screening and agree to one of the following:
- •Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
- •Consistent and correct use of one of the following acceptable methods of birth control:
- •Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.
- •Implants of levonorgestrel.
- •Injectable progestogen.
Exclusion Criteria
- •A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- •Pregnant or lactating females.
- •Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy for metastatic disease.
- •Prior therapy with ErbB1 and/or ErbB2 inhibitors.
- •Concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking study medication.
- •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.
Arms & Interventions
Single arm
Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Subjects will be treated with paclitaxel for at least 6 months, and may continue on paclitaxel at the discretion of the Investigator, or discontinued sooner if the subject has disease progression, an unacceptable toxicity or withdraws consent.
Intervention: Lapatinib oral tablets
Single arm
Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Subjects will be treated with paclitaxel for at least 6 months, and may continue on paclitaxel at the discretion of the Investigator, or discontinued sooner if the subject has disease progression, an unacceptable toxicity or withdraws consent.
Intervention: Paclitaxel infusion
Outcomes
Primary Outcomes
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)
Time Frame: From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)
OR is defined as the number of participants achieving either a CR or PR, per Response Evaulation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.
Secondary Outcomes
- Duration of Response (DoR), as Assessed by the IRC(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 Week 86))
- Duration of Response (DoR), as Assessed by the Investigator(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 Week 86))
- Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator(From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86))
- Time to Response, as Assessed by the IRC(From randomization until the first documented evidence of a PR or CR (up to Week 86))
- Time to Response, as Assessed by the Investigator(From randomization until the first documented evidence of a PR or CR (up to Week 86))
- Time to Progression, as Assessed by the IRC and the Investigator(From the start date of treatment until the date of radiological disease progression or the date of death due to breast cancer (up to Week 86))
- Progression-free Survival, as Assessed by the IRC and the Investigator(From the start date of treatment until the date of radiological disease progression or death due to any cause, whichever occurs first (up to Week 86))
- Overall Survival(From the date of the first dose until the date of death due to any cause (up to Week 86))
- Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)(From the start of study medication until 28 days after the last dose (up to Study Week 381))