E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
|
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 compare the time to disease progression (TTP) in patients with HER2 positive metastatic breast cancer and progression after a previous 1st-line chemotherapy plus trastuzumab treatment randomized to continuation or discontinuation of trastuzumab in combination with 2nd-line chemotherapy. |
|
E.2.2 | Secondary objectives of the trial |
• To compare the objective response rate (ORR) between the two arms • To compare the clinical benefit (CR + PR + SD) between the two arms • To evaluate the time to treatment failure (TTF) • To evaluate the safety on the two arms • To compare overall survival (OS) between the two arms |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written and signed informed consent prior to beginning specific protocol procedures showing the patients’ willingness and awareness to participate in the trial and comply with its proceedings. 2. Female patients 3. Age >18 years. 4. Pathologically confirmed and documented metastatic breast cancer. 5. Documented HER2-overexpression of the primary or metastatic tumor tissue detected by immunohistochemistry (IHC 3+) and/or genamplification detected by FISH. 6. Disease progression during or after a previous 1st-line chemotherapy* plus trastuzumab treatment as follows: • Either of taxanes (docetaxel or paclitaxel) + trastuzumab given as 1st-line therapy for palliation • Other allowed chemotherapy drugs combined with trastuzumab in 1st-line setting: vinorelbine, gemcitabine, capecitabine, platinum compounds, cycylophosphamide, methotrexate, fluorouracil. 7. Patients are scheduled to receive an effective 2nd-line chemotherapy as per standard medication care. Schedule and dose as investigators’ opinion in the best interest of the patients. 8. Treatment free interval of trastuzumab between 1st-line and 2nd-line administration is a maximum of 6 weeks. 9. At least 4 weeks since major surgery with full recovery. 10. At least 4 weeks since radiotherapy with full recovery. 11. Complete radiology and tumor measurement work up within 5 weeks prior to randomization. 12. Laboratory: neutrophils count ≥ 1,5 x 109/L, platelet ≥ 100 x 109/L, bilirubin =or< 2 x the upper limit of normal for the institution (ULN), SGOT/SGPT =or<2,5 x ULN or < 5 x ULN for patients with liver metastases, creatinine =or<2.0 mg/dl (within 3 weeks prior to randomization). 13. Left ventricular ejection fraction (LVEF) by cardiac ultrasound or MUGA of ≥50% within 3 weeks prior to randomization. 14. If of childbearing potential, pregnancy test – either urine or serum test - is negative within 1 week prior to randomization. In addition the patient agrees to use an effective method to avoid pregnancy during the study. 15. ECOG performance status =or<2 and life expectancy ≥12 weeks (see Appendix 2) 16. Patients must be accessible for treatment and follow-up. 17. Patients entering the trial must be treated and followed at the participating center.
|
|
E.4 | Principal exclusion criteria |
1. Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency. 2. Concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive or replacement therapy). 3. Anthracyclines as a part of the previous 1st-line chemotherapy or the planned 2nd-line chemotherapy. 4. Known anamnestic history (or present condition) of parenchymal brain metastases. 5. Prior history of myocardial infarction within the previous 6 months. 6. Unstable angina pectoris, uncontrolled arrhythmia and cardiac insufficiency (NYHA Class III-IV) at the time of inclusion. 7. Cardiac toxicity during the previous 1st-line chemotherapy plus trastuzumab treatment indicating discontinuation of Herceptin® administration. 8. Serious rest dyspnoe in connection with the advanced malignant process claiming supportive oxygen therapy. 9. Pleural effusion, unless clinically controllable. 10. Serious intercurrent medical conditions that may interfere with the planned treatment (including AIDS, serious active infection, CNS disease, psychiatric illness). 11. History of other malignancy within the last 5 years, which could affect the diagnosis or assessment of breast cancer. 12. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening. 13. Pregnant or nursing women. 14. Patients who in opinion of investigator are ineligible for 2nd-line chemotherapy.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
2nd line chemotherapy without Herceptin as per standard medical care |
|
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
|
Recruitment is estimated to take up to 2 years. Efficacy (response rate) will be assesed for up to one year after the last patient is recruited - or until disease progression (whichever will happen earlier). So the study will take 3 years. Patients with progression or withdrawal will be followed (adverse events and survival) up to one year following enrolment period. |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |