A Phase II, Randomised, Multi-Centre Study Evaluating Lapatinib in Combination With Vinorelbine or Capecitabine in Women With ErbB2 Overexpressing Metastatic Breast Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 112
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS) in the Randomized Phase
Study Overview
Brief Summary
This is a randomized, parallel-arm, open-label, multi-centre, Phase II study to determine the efficacy and safety of lapatinib in combination with vinorelbine or capecitabine in women with ErbB2 overexpressing metastatic breast cancer (MBC) who have received no more than one chemotherapeutic regimen in the metastatic setting.
Detailed Description
Approximately 105 subjects will be enrolled in the study and randomized 2:1 to one of the following regimens Arm A (n=70): Lapatinib 1250 mg orally once daily continuously plus Vinorelbine 20mg/m2 intravenously (IV) on day 1 and 8, every third week, or Arm B (n=35): Lapatinib 1250 mg orally once daily (QD) continuously plus Capecitabine 2000 mg/m2/day orally in 2 doses 12 hours apart on days 1-14 every third week. Randomization will be stratified according to the following variables: 1) Prior receipt of therapy for metastatic breast cancer (Yes or No), and 2) Site of metastatic disease (Visceral/Soft tissue or Bone-only). Subjects will receive randomized study treatment until disease progression or discontinuation of study treatment due to unacceptable toxicity, withdrawal of consent, lost to follow up, or death. All subjects who discontinue study treatment without documented progression will continue to be followed for progression according to protocol-schedule until new anti-cancer therapy is initiated and/or progression or death is documented. Survival data will be collected for all subjects to ensure a minimum of 18 months survival data. This study will include a safety run-in phase for approximately the first 30 subjects (20 randomized to lapatinib and vinorelbine; 10 to lapatinib and capecitabine).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Subjects taking prohibited medications are not eligible for the study.
- •Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this study.
- •Prior therapy with more than one chemotherapeutic regimen for metastatic breast cancer.
- •Concurrent anticancer or concomitant radiotherapy treatment.
- •History of uncontrolled or symptomatic angina; history of arrhythmias requiring medications ; clinically significant myocardial infarction < 6 months from study entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below the institutional normal limit; or any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
- •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).
- •Use of an investigational drug within 30 days or 5 half - lives, whichever is 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 immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients that in the opinion of the investigator or GSK Medical Monitor contraindicates their participation.
- •Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD).
- •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 limit compliance with study requirements.
- •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.
- •Pregnant or lactating females at any time during the study (due to the potential teratogenic or abortifacient effects of lapatinib and breastfeeding).
- •Subjects with diseases affecting gastrointestinal function resulting in an inability to take oral medication , including ; malabsorption syndrome, disease significantly affecting gastrointestinal function , or resection of the stomach , small bowel , or colon. Subjects with inflammatory bowel disease or ulcerative colitis are also excluded.
- •Peripheral neuropathy of Grade 2 or greater.
- •Unresolved or unstable, serious toxicity from prior administration of another investigational drug and / or of prior cancer treatment.
- •Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
Arms & Interventions
Lapatinib + Vinorelbine
Lapatinib + Vinorelbine
Intervention: Vinorelbine (Drug)
Lapatinib + Vinorelbine
Lapatinib + Vinorelbine
Intervention: Lapatinib (Drug)
Lapatinib + Capecitabine
Lapatinib + Capecitabine
Intervention: Lapatinib (Drug)
Lapatinib + Capecitabine
Lapatinib + Capecitabine
Intervention: Capecitabine (Drug)
Outcomes
Primary Outcomes
Progression Free Survival (PFS) in the Randomized Phase
Time Frame: From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)
PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. PD is defined as at least a 20 % increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of \>=1 new lesion.
Secondary Outcomes
- Time to Response in the Randomized Phase(From randomization until the time of the first documented confirmed CR or PR (average of 27 study weeks))
- Number of Participants With Clinical Benefit (CB) in the Randomized Phase(From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks))
- Area Under the Concentration-time Curve Over the Dosing Interval (AUC-tau) for Vinorelbine(Days 1 and 8; 0 to 24 hours post-dose)
- Maximum Concentration (Cmax) for Vinorelbine(Days 1 and 8; 0 to 24 hours post-dose)
- Number of Participants With Grade 4 and Grade 5 Adverse Events (AE)(From randomization until disease progression, death, or discontinuation from the study (average of 55 study weeks))
- Number of Participants With Overall Response (OR), as Assessed by the Investigator in the Randomized Phase(From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks))
- Overall Survival (OS)(From the date of randomization until death (average of 55 study weeks))
- Duration of Response (DOR) in the Randomized Phase(From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 27 study weeks))