Phase I/II study of lapatinib in combination with paclitaxel as 1L chemotherapy for ErbB2-positive MBC
Trial overview
Number of Participants with intolerable toxicities in Phase I of the Study
Timeframe: 28 days
Overall survival
Timeframe: From the start of treatment until death due to any cause or study close, whichever occurred first (assessed up to a maximum of 1290 Days)
Progression-free Survival (PFS)
Timeframe: From the start of treatment until the earliest date of radiological disease progression or death due to any cause, whichever occured first (up to 1009 Days).
Time to response
Timeframe: From the start of treatment until the first documented evidence of a PR or CR, whichever status is recorded first (up to 66 Days).
Duration of response
Timeframe: From the first documented evidence of a CR or a PR until the first documented sign of disease progression or death, whichever occurred earlier (up to 953 Days).
Number of partcipants with a best overall Response (OR) as determined by the Response Evaluation Criteria in Solid Tumors (RECIST)
Timeframe: From the start of treatment until progressive disease/death (up to 1009 Days).
Number of participants with clinical benefit response (CBR)
Timeframe: From the start of treatment until progressive disease/death (up to 1009 Days).
Maximum Plasma Concentration (Cmax) of lapatinib and paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel
Area Under the Concentration-time Curve (AUC) (0-24) of lapatinib and paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel
AUC from Time Zero to Infinity (0-INF) of paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel
Time to the maximum drug concentration (Tmax) of lapatinib and paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel
Distribution Volume at Steady State (Vss) of paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel
Half-life (t1/2) of paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel
Drug clearance (CL) of paclitaxel
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel
Participation criteria
- Prior written consent in participating in the study by the subject or his/her private attorney.
- Japanese female >=18 years of age.
- Pregnant or lactating females at anytime during the study.
- Received prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy for metastatic disease.
- Prior written consent in participating in the study by the subject or his/her private attorney.
- Japanese female >=18 years of age.
- Invasive breast cancer with stage IV disease.
- Documentation by local laboratory of ErbB2 status by immunohistochemistry (IHC) or amplification by fluorescence in situ hybridization (FISH).
- If a taxane had been administered in the neoadjuvant or adjuvant setting, progression must have occurred >12 months after completion of this treatment and the patients recovered from all associated toxicities.
- Measurable lesion(s) according to RECIST criteria.
- 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.
- Patient with visceral disease that requires chemotherapy (e.g., patients with liver or lung metastases).
- Rapidly progressing or life threatening disease that are considered to be inapplicable to hormonal therapy, 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.
- Subjects recovered from all the associated toxicities by prior endocrine therapy.
- Eastern cooperative oncology group (ECOG) Performance status (PS) of 0 or 1.
- Able to swallow and retain oral medication.
- Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scan is accepted in cases where an echocardiogram cannot be performed or is inconclusive.
- Adequate organ function.
For those patients whose disease is ER+ and/or PR+ one of the following criteria should be met:
- Pregnant or lactating females at anytime during the study.
- Received prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy for metastatic disease.
- History of other malignancy.
- Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab, in the adjuvant setting.
- Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment.
- Used an investigational drug within 30 days or five half-lives, whichever is longer, preceding the first dose of investigational treatment.
- Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior anti-cancer treatment.
- Uncontrolled infection.
- Patients having at least positive antibody either to HBs or HBc.
- Patients who have had a positive HCV antibody.
- Peripheral neuropathy 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.
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
- 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.
- Known history or concurrent condition of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
- Concurrent treatment with prohibited medications.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel or lapatinib or their excipients.
- Have current 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).
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.