Overview
Safety and Efficacy of Lapatinib Plus Trastuzumab or Lapatinib Plus Capecitabine in Metastatic Breast Cancer
Status:
Withdrawn
Withdrawn
Trial end date:
2015-03-01
2015-03-01
Target enrollment:
0
0
Participant gender:
Female
Female
Summary
The purpose of this study is to estimate the clinical benefit of lapatinib plus trastuzumab compared to lapatinib plus capecitabine as measured by investigator-assessed progression-free survival, tumour response and overall survival.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.Collaborator:
OnkoDataMed GmbHTreatments:
Capecitabine
Lapatinib
Trastuzumab
Criteria
Inclusion Criteria:1. Histologically confirmed and metastatic breast cancer.
2. Hormone receptor-negative patients
3. HER2-positive tumours with 3+ intensity on IHC staining for HER2 or amplification of
the HER2 gene on ISH.
4. Patients must have measurable metastatic disease by RECIST v1.1 with radiologic scans
within 28 days of study registration.
5. Prior anti-HER based therapy:
- Received at least 1 but no more than 2 prior anti-HER2 based regimens for
metastatic disease.
- Prior treatment with trastuzumab-DM1 (TDM1) is allowed (T-DM1 represents one line
of anti-HER2 and one line of chemotherapy).
- Radiological evidence of confirmed progressive disease per RECIST while receiving
trastuzumab as a single agent or in combination with chemotherapy for at least 6
weeks either as first line or second line therapy, for an interval of at least 6
weeks at any time.
- Prior treatment with Lapatinib is permitted provided that at least 6 month have
elapsed since the last dose.
6. Prior chemotherapy with anthracyclines and taxanes (unless clinically contraindicated,
which must have been documented).
7. Patients must have the following laboratory values:
- Absolute Neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- AST and ALT ≤ 2.5 x ULN
- Bilirubin level ≤ 1.25 X ULN
- Serum creatinine < 1.5 X ULN or calculated creatinine clearance ≥ 40ml/min
8. Normal cardiac function with a left ventricular ejection fraction of at least 50% (as
assessed by quantitative echocardiogram)
9. ECOG performance status 0-1
10. Age ≥ 18 years
11. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
including any female who has had hysterectomy, a bilateral oophorectomy, bilateral
tubular ligation or is post-menopausal (total cessation of menses for ≥ 1 year; if the
patient is of childbearing potential, she must have a negative serum pregnancy test
within 2 weeks prior to the first dose of study treatment, preferably as close to the
first dose as possible, and agrees to use adequate contraception (for example,
intrauterine device [IUD], birth control pills unless clinically contraindicated, or
barrier device) beginning 2 weeks before the first dose of investigational product and
for 28 days after the final dose of investigational product.
12. Written informed consent prior to admission to this study.
Exclusion Criteria:
1. Patients with confirmed brain metastases or a history of primary central nervous
system tumours or who have signs/symptoms attributable to brain metastases and have
not been assessed with radiologic imaging to rule out the presence of brain
metastases. Patients with treated brain metastases that are asymptomatic and have been
clinically stable for 3 months will be eligible for protocol participation.
2. Hormone receptor-positive patients
3. Prior treatment with lapatinib within the last 6 months.
4. More than 2 lines of trastuzumab-based treatment for advanced disease.
5. Significant cardiovascular disease, such as
- History of myocardial infarction, acute coronary syndromes (including unstable
angina), or history of coronary angioplasty/stenting/bypass grafting within past
6 months.
- History of symptomatic congestive heart failure (CHF) New York Heart Association
(NYHA) Classes II-IV or LVEF <50% by ECHO.
- Severe cardiac arrhythmia requiring medication or severe conduction
abnormalities.
- Poorly controlled hypertension (resting diastolic blood pressure >100 mmHg)
- Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy,
or cardiomyopathy.
6. QTc prolongation defined as a QTc interval > 460 msec or other significant ECG
abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia
(ventricular rate < 50 beats/min)
7. Subjects who have current active hepatic or biliary disease or severe hepatic
impairment (with exception of patients with Gilbert's syndrome, asymptomatic
gallstones, liver metastases or stable chronic liver disease per investigator
assessment)
8. Malabsorption syndrome or other condition that would interfere with enteral absorption
9. Hypersensitivity to trastuzumab, murine proteins or to any of the excipients.
10. Severe dyspnoea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
11. History of severe and unexpected reactions to fluoropyrimidine therapy.
12. Hypersensitivity to capecitabine or to any of the excipients or fluorouracil.
13. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
14. Severe leucopenia, neutropenia or thrombocytopenia.
15. Severe renal impairment (creatinine clearance < 40 ml/min.).
16. Treatment with sorivudine or its chemically related analogues, such as brivudine.
17. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that, in the investigator's opinion, gives reasonable suspicion of
a disease or condition that contraindicates the use of an investigational drug, may
affect the interpretation of the results, render the patient at high risk from
treatment complications or interferes with obtaining informed consent.
18. Contraindications to any of the medicinal products in the combination regimen.
19. Psychological, familial, sociological or geographical conditions that do not permit
compliance with the study protocol.
20. Patients accommodated in a closed institution by authority or court order.
21. Concurrent treatment with other experimental drugs. Participation in another clinical
trial with any investigational drug within 30 days prior to study entry.