This is an open-label, randomized, parallel group Phase 2A/2B study to evaluate the clinical activity of ASLAN001 in combination with capecitabine compared with lapatinib in combination with capecitabine in patients with HER2 positive metastatic breast cancer that has failed on prior trastuzumab therapy.
Phase 2A Design: The Phase 2A part is an open-label, randomized, parallel group study using tumor size as its primary efficacy endpoint. Approximately 44 eligible patients will be randomized in a 1:1 ratio to receive either ASLAN001 400 mg orally twice daily (BID) or lapatinib 1250 mg orally once daily (QD), both on a background of capecitabine 1000 mg/m2 orally BID for Days 1-14 of a 21-day cycle. Radiological imaging to assess disease status will be performed at baseline and every 6 weeks until disease progression (as assessed by the Investigator). Patients who have not experienced disease progression after 12 weeks may continue to receive randomized therapy and will continue to have radiological scans every 6 weeks until disease progression. Criteria to Proceed to Phase 2B: In the absence of any safety or tolerability concerns, continuation to the Phase 2B part of the study will be primarily based on the statistical comparison of the percentage change in tumor size from baseline to Week 12 and a one-sided p-value \<0.1 in favor of the ASLAN001-containing treatment arm would be supportive of continuation to Phase 2B. Phase 2B Design: The Phase 2B part of the study will continue to recruit if the pre-specified efficacy criteria are met in the Phase 2A part and if the tolerability of ASLAN001 in combination with capecitabine is considered acceptable. The Phase 2B part is an open-label, randomized, parallel group study. In this part, approximately 160 patients will be randomized in a 1:1 ratio to receive either ASLAN001 400 mg BID or lapatinib 1250 mg QD, both in combination with capecitabine 1000 mg/m2 BID for Days 1-14 of a 21-day cycle.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
ASLAN001 400mg BID
Lapatinib 1250mg QD
Capecitabine 1000mg/kg BID days 1-14 of a 21-day cycle
Australia
Western Australia, Australia
Hong Kong
Hong Kong, Hong Kong
New Zealand
Christchurch, New Zealand
To compare the efficacy of ASLAN001 in combination with capecitabine, to lapatinib in combination with capecitabine in the percentage change from baseline tumor size at Week 12
Time frame: Week 12
Safety for all metastatic breast cancer (MBC) subjects (Physical examination, body weight, vital signs, ECG parameter, hematology, clinical laboratory tests and Adverse Events)
Physical exam, body weight, vital signs (Blood pressure, respiratory rate and body temperateure), ECG parameter, hematology, clinical laboratory tests (clinical chemistry, coagulation and urinalysis) and Adverse Events (AEs)/ Serious Adverse Events (SAEs)
Time frame: estimated 2 years
To further compare the efficacy of ASLAN001 in combination with capecitabine to lapatinib in combination with capecitabine, as measured by PFS and tumor volume
Time frame: Week 12
To further compare the efficacy of ASLAN001 in combination with capecitabine to lapatinib in combination with capecitabine, as measured by the Objective Response Rate (ORR), Duration of Response (DoR), and Overall Survival (OS)
Composite outcome measures
Time frame: 2 years
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New Zealand
Tauranga, New Zealand
Philippines
Bacolod City, Philippines
Philippines
Dasmariñas, Philippines
Singapore
Singapore, Singapore
Singapore
Singapore, Singapore
South Korea
Seoul, South Korea
South Korea
Seoul, South Korea
...and 9 more locations