LPT 111111- A Single-arm, Multicenter Phase II Study to Evaluate The Combination of Weekly Nanoparticle Albumin Bound Paclitaxel (Nab-Paclitaxel or ABRAXANE®) and Lapatinib (TYKERB®) in Women With No More Than One Prior Treatment for ErbB2 Overexpressing Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Overall Tumor Response (OR)
Overview
Brief Summary
This was an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Sixty subjects were to be enrolled in the study. Subjects were to receive nab-paclitaxel (100 mg/m2 intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle) plus lapatinib (1000 mg once daily). Subjects were to receive treatment until disease progression or withdrawal from the study. The primary objective of this study was to evaluate overall tumor response rate of lapatinib in combination with nab-paclitaxel administered in women with ErbB2 overexpressing MBC who received no chemotherapeutic regimen in the metastatic setting. Secondary objectives included progression-free survival, overall survival, duration of response, time to response and time to progression and safety. Safety and efficacy assessments were to be performed at 8 and 12 week intervals, and at the end of treatment.
Subject: Metastatic Breast Cancer, ErbB2, First-line therapy, Lapatinib, Nab-paclitaxel
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •A subject was eligible for inclusion in this study only if all of the following criteria apply:
- •Subjects must have histologically confirmed invasive breast cancer with Stage IV disease at primary diagnosis or at relapse after curative-intent surgery. Where the disease was restricted to a solitary lesion, the neoplastic nature of the lesion should have been confirmed by cytology or histology.
- •Documented amplification of ErbB2 3+ by immunohistochemistry or a positive score (\>2.2) by FISH using a local laboratory result (which was considered sufficient in this study with no further verification by a central laboratory).
- •Subjects must have received no more than one prior chemotherapeutic regimen in the metastatic setting.
- •If a taxane had been administered in the neoadjuvant, adjuvant or metastatic setting, progression must have occurred ≥12 months after completion of this treatment.
- •Prior therapy with radiation for this breast cancer population was permitted if it was administered in the neoadjuvant or adjuvant non metastatic setting. Radiotherapy given in the metastatic setting, prior to initiation of study medication, was allowed to a limited area (e.g., palliative therapy and involving less than 25% of bone marrow), if it was not the sole site of disease. Subjects must have completed radiation treatment and recovered from all acute radiation treatment related toxicities (e.g., bone marrow suppression) prior to commencement of combination treatment.
- •The subject must have received all prior chemotherapy treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities. Subjects who have received weekly dose of prior chemotherapy e.g. gemcitabine or capecitabine may enroll 2 to 3 weeks after cessation of treatment provided that they have recovered from all related toxicities.
- •Prior therapy with trastuzumab in the neoadjuvant, adjuvant or metastatic setting was permitted. The subject must have received all prior trastuzumab treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities.
- •Prior endocrine therapy was permitted in the neoadjuvant or adjuvant or metastatic setting. The subject must have received all prior endocrine treatment at least 1 week prior to enrollment in this study and must have recovered from all related toxicities.
- •Prior diagnosis of cancer was allowed as long as the subject was free of disease for 5 years. Subjects with completely resected basal or squamous cell skin cancer, thyroid cancer or successfully treated cervical carcinoma in-situ were allowed if it had been 1 year or greater since definitive surgery.
Exclusion Criteria
- •A subject was not be eligible for inclusion in this study if any of the following criteria apply:
- •Subjects who received more than one prior chemotherapeutic regimen in the metastatic setting
- •Subjects taking treatment with medications provided in the list of restricted medications and substances in the drug information section for lapatinib were not eligible for the study. This included human immunodeficiency virus-positive subjects receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with lapatinib.
- •Prior treatment with lapatinib.
- •Concurrent anticancer or concomitant radiotherapy treatment;
- •Concurrent treatment with prohibited medications;
- •Use of an investigational drug within 30 days or 5 half-lives, whichever was longer, preceding the first dose of investigational treatment, or, concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents.
- •Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or nab-paclitaxel or excipients;
- •Known history of uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements.
- •Had active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Arms & Interventions
Single Arm
Single arm combination therapy of Lap and NabPaclitaxel combination
Intervention: Lapatinib/nab-Paclitaxel (Drug)
Outcomes
Primary Outcomes
Overall Tumor Response (OR)
Time Frame: Start of treatment to disease progression or death or discontinuation from study or at least 28 days after last dose (up to Week 131)
OR was defined as the percentage of participants experiencing either a confirmed complete response (CR) or a confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0. CR is defined as the disappearance of all lesions (target and/or non-target). PR is defined as at least a 30% decrease in the sum of the longest dimensions (LD) of target lesions taking as a reference the baseline sum LD, with non-target lesions not increased or absent.
Secondary Outcomes
- Overall Survival (OS)(Start of treatment to death (up to Week 131))
- Time to Progression (TTP)(Start of treatment to disease progression or death (up to Week 131))
- Progression-Free Survival (PFS)(Start of treatment to disease progression or death (up to Week 131))
- Duration of Response (DOR)(First documented response (CR or PR) to disease progression or death (up to Week 131))
- Time to Response (TTR)(Start of treatment to first documented response (CR or PR) (up to Week 131))