E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically confirmed breast cancer, overexpressing HER2, that has led to neoplastic meningitis. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006202 |
E.1.2 | Term | Breast cancer stage IV |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of the study treatment, as measured by the overall CNS response rate. |
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E.2.2 | Secondary objectives of the trial |
To determine in the study population the time to progression, the time to neurological progression, the time to systemic progression, the sytemic clinical benefit rate and the overall survival rate; to assess the toxicity of the study treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient has provided her written informed consent to take part in the study. 2. The patient has a histologically confirmed diagnosis of unilateral or bilateral breast cancer. 3. The patient's tumour overexpresses HER2, as shown by either of the following: – IHC test result: 3+ – IHC test result 2+, confirmed by a positive result of a FISH assay. 4. The patient should have been treated with anthracyclines and taxanes and trastuzumab. 5. The patient has neoplastic meningitis, as demonstrated EITHER by a positive lumbar CSF (cerebralspinal liquor) cytology OR by the presence of characteristic signs and symptoms of neoplastic meningitis supported by an MRI scan indicating the presence of meningeal tumour. [Note: The additional presence of parenchymal brain metastases does NOT affect the patient's eligibility for inclusion in the study.] 6. The patient has normal cardiac function, as demonstrated by both ECG (no clinically relevant findings) and echocardiogram (LVEF ≥ 50%) 7. The patient has adequate organ function, defined by the following laboratory values, all of which must be within the respective range specified: Haematology: Absolute neutrophil count 1,5 109/L Haemoglobin 9 g/dL Platelets 100 109/L Hepatic: Albumin 2.5 g/dL Serum bilirubin 1, 5 x ULN unless due to Gilbert’s syndrome AST and ALT 3 ULN if no liver metastases are documented 5 ULN if liver metastases are documented Renal: Serum creatinine 1.5 mg/dL Creatinine clearance 50 mL/min (calculated by the method of Cockcroft and Gault) 8. If of child-bearing potential, the patient is willing to use appropriate contraception. 9. The patient has a WHO/ECOG performance status of 0 or 1. 10. Life expectancy of at least 12 weeks 11. Able to swallow and retain oral medications 12. Prior radiotherapy due to brain metastasis is allowed 13. Whole brain radiation therapy (WBRT) or stereotactical radiosurgery (SRS) due to new brain metastasis and neoplastic meningitis is only allowed, if there is an additional symptom pressure with extracranial location of meningeosis.
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E.4 | Principal exclusion criteria |
1. The patient is pregnant (urine HCG test at screening) or lactating. 2. The patient has had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrolment, or there is an anticipated need for a major surgical procedure during the course of the study. 3. The patient has Class II, III or IV heart failure as defined by the NYHA functional classification system. 4. The patient has had an arterial or venous thrombosis, including stroke, transient ischemic attack, or cerebrovascular accident within the last six months. 5. The patient has had a myocardial infarction, unstable angina, cardiac angioplasty or stenting procedure within the last six months. 6. The patient has history of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Subjects with ulcerative colitis or an unresolved bowel obstruction are also excluded. 7. The patient has, apart from the study indication, any other history of malignancy within the past 10 years, except adequately treated basal cell tumor or in-situ carcinoma of the cervix uteri. 8. The patient has a concurrent disease or condition that in the opinion of the investigator would compromise her safety as a subject in the trial or would prevent her from receiving the study treatments. 9. The patient has any psychological, family or sociological conditions that do not permit compliance with the protocol. 10. The patient requires concurrent cancer therapy (chemotherapy, radiation therapy, biological therapy, immunotherapy, or hormonal therapy) while on study. 11. The patient requires concurrent treatment with an investigational agent, participation in another clinical trial, or any specifically prohibited medication while on study. 12. The patient has any known (immediate or delayed) hypersensitivity reaction to, or inability to tolerate, drugs chemically related to lapatinib, capecitabine of cytarabine or the constituents of the preparations to be administered in this study. 13. The patient has received prior intrathecal therapy 14. Any presence of one or more of the following disorders: Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia. 15. Treatment with lapatinib is contra-indicated. 16. Treatment with capecitabine is contra-indicated 17. Treatment with DepoCyte® is contra-indicated. 18. The patient is currently taking part in another interventional clinical trial or has done so within the last three months. 19. Active Infection
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the efficacy of the study treatment, as measured by the overall CNS response rate. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |