Phase I/II Study of Lapatinib in Combination With Paclitaxel as 1L Chemotherapy for ErbB2-positive MBC

NCT01138046 | Completed Phase 2 Results

• 1 other identifier: 113806
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 10

Brief Summary

This is an open-label, non-randomized, multi-center study of lapatinib plus paclitaxel to evaluate safety, tolerability and efficacy in Japanese patients with ErbB2 over expressing advanced or metastatic breast cancer. Lapatinib 1500mg/day will be administered in combination with paclitaxel 80mg/m2/week. Lapatinib and paclitaxel will be administered until disease progression or withdrawal from the study due to unacceptable toxicity. The study will proceed in two phases. The first phase (Phase I part) will lead to evaluate safety and tolerability of lapatinib taken together with paclitaxel in the first 6 subjects. Pharmacokinetic profile also will be evaluated as the secondary objects. Then the study will move to the next treatment phase (Phase II part) to evaluate further safety and clinical activity, if no major safety concerns are raised during Phase I part. The primary objective of the study is to evaluate overall survival (OS), and the secondary objectives are Objective tumour response rate (ORR), Duration of response, Time to response, Clinical benefit and Progression-free survival (PFS) in 12 subjects.

Conditions

Neoplasms, Breast

Keywords

advanced/metastatic breast cancer; lapatinib; ErbB2; ErbB2-overexpressing; pharmacokinetics; dual kinase inhibitor; HER-2/neu; EGFR; ErbB1

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Intolerable Toxicities in Phase I of the Study

  Investigational treatment was considered tolerable if one or more of the tolerability criteria were met by none or one of the 6 participants in the first cycle of Phase I. If one or more tolerability criteria were met by two or more participants, the issue was referred to the safety committee. Tolerability criteria for toxicities related to investigational treatment included grade 4 neutropenia persisting for 7 or more days, thrombocytopenia with a platelet count of less than or equal to 25,000/millimeter (mm)\^3 , clinically significant Grade 3 or 4 non-haematologic toxicities (excluding nausea) and inability to start cycle 2 within 2 weeks of scheduled dosing due to unresolved toxicity.

  28 days

• Overall Survival

  Overall survival is defined as the time from the start of treatment until death due to any cause. For participants who survived, time to death was censored at the time of the last confirmation of survival.

  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)

Secondary Outcomes (12)

• Progression-free Survival (PFS)

  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

  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

  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)

  From the start of treatment until progressive disease/death (up to 1009 Days).

• Number of Participants With Clinical Benefit Response (CBR)

  From the start of treatment until progressive disease/death (up to 1009 Days).

Study Arms (1)

Lap+weekly Pacli

EXPERIMENTAL

These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib. Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent.

Drug: Lapatinib in combination with weekly paclitaxel

Interventions

Lapatinib in combination with weekly paclitaxel DRUG

These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib (1500 mg once daily, starting on the second day of phase I). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Study completion is defined as deaths after administering study treatment for more than once. Subjects will be treated with paclitaxel for standard of 6 cycles, and may be continued at the discretion of investigators. If the subject experiences progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib therapy, paclitaxel therapy must be terminated any time of study period, even before 6 cycles of paclitaxel are given.

Lap+weekly Pacli

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• For those patients whose disease is ER+ and/or PR+ one of the following criteria should be met:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (10)

GSK Investigational Site

Aichi, 464-8681, Japan

Location

GSK Investigational Site

Ehime, 791-0280, Japan

Location

GSK Investigational Site

Hyōgo, 673-8558, Japan

Location

GSK Investigational Site

Kagoshima, 892-0833, Japan

Location

GSK Investigational Site

Kanagawa, 241-8515, Japan

Location

GSK Investigational Site

Osaka, 540-0006, Japan

Location

GSK Investigational Site

Osaka, 565-0871, Japan

Location

GSK Investigational Site

Saitama, 350-1298, Japan

Location

GSK Investigational Site

Saitama, 362-0806, Japan

Location

GSK Investigational Site

Tokyo, 113-8677, Japan

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2010
• First Posted: June 7, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 7, 2014
• Results First Posted: September 19, 2014

Record last verified: 2014-09

Locations

JP (10)