A randomised phase II screening trial with functional imaging and patient reported toxicity sub-studies comparing LApatiNib plus capecitabine versus continued Trastuzumab plus capecitabine after local therapy in patients with ERb B2 positive metastatic breast cancer developing braiN metastasis /es - LANTER
- Conditions
- Patients with ERB B2 positive metastatic breast cancer developing brain metastasis/es
- Registration Number
- EUCTR2010-022737-28-GB
- Lead Sponsor
- eeds Teaching Hospitals NHS Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 30
1. Male or female aged = 18 years 2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 3. Given written informed consent prior to any trial specific procedures 4. Expected survival = 12 weeks 5. Histologically or cytologically confirmed invasive breast cancer, with Stage IV disease including newly diagnosed CNS metastasis/es 6. ErbB2 overexpression in the invasive component of the primary or metastatic lesion as locally defined by: • 3+ staining by immunohistochemistry (IHC); • or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH; • or ErbB2 gene amplification by FISH; Participants with a negative or equivocal overall result are not eligible for inclusion in the trial. 7. Evidence of metastatic brain disease. To be considered evaluable for the primary endpoint and the CNS response rates endpoints, participants must have at least one measurable brain lesion that can be accurately measured in at least one dimension (shortest dimension to be recorded) as >20mm with conventional techniques or as >10mm with spiral CT scan (see appendix X for the evaluation of measureable disease). Participants with leptomeningeal disease are not eligible for participation in the trial due to the lack of measurable disease. 8. Treated previously with taxanes or anthracyclines in the adjuvant or metastatic setting. All treatment related adverse events must be = Grade 1 at the time of randomisation. 9. Prior treatment with trastuzumab is required and all treatment related adverse events must be = Grade 1 at the time of randomisation 10. Completed local cranial therapy (Stereotactic Radio Surgery or Whole Brain Radiotherapy) 11. Able to swallow and retain oral medication 12. Normal organ and bone marrow function as defined below: • Leukocytes >3,000/µL • Absolute neutrophil count >1,500/µL • Platelets >100,000/µL • Total bilirubin within normal institutional limits • AST (SGOT)/ ALT (SGPT) =2.5 X institutional upper limits of normal • Creatinine within normal institutional limits or creatinine clearance =60ml/min/ 1.73m2 for participants with creatinine levels above institutional normal. 13. Cardiac ejection fraction =50% or within the institutional limit as measured by echocardiogram or MUGA scan. Note that the baseline and on treatment scan should be performed using the same modality and preferably the same institution.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
1. Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab 2. Prior treatment with capecitabine 3. Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of cancer 4. Known dihydropyrimidine dehydrogenase (DPD) deficiency 5. Current active hepatic or biliary disease (with exception of participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 6. Pregnant or lactating females. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to trial entry and for the duration of the trial participation. 7. History of significant non-breast malignancy (aside from non-melanomatous skin cancer, carcinoma in situ of the uterine cervix, superficial bladder cancer treated with curative intent) 8. History of allergic reactions attributed to compounds of a similar chemical or biological composition as to lapatinib 9. Uncontrolled inter-current illness including, but not limited to: • ongoing or active infection • symptomatic congestive heart failure • unstable angina pectoris • cardiac arrhythmia • psychiatric illness/social situations that would limit compliance with trial requirements 10. GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn’s, ulcerative colitis). 11. Renal function as measured by creatinine clearance <30ml/min (ratio to norm <0.1) 12. Not recovered from adverse events due to agents administered more than 4 weeks earlier with the exception of adverse events =grade 1 after previous chemotherapy 13. Prior treatment with EGFR targeting therapies 14. Active cardiac disease, defined as: • History of uncontrolled angina • History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation • Myocardial infarction < 6 months from trial entry • Uncontrolled or symptomatic congestive heart failure • Ejection fraction below 50% or the institutional lower normal limit • Any other cardiac condition, which in the opinion of the treating investigator, would make this protocol unreasonably hazardous for the participant 15. Any concomitant medications or substances forming part of normal ongoing care locally known to affect, or have the potential to affect, the activity or pharmacokinetics of lapatinib.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method