E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic 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 make a preliminary assessment of the efficacy of pertuzumab in combination with Herceptin® in patients who have progressed on Herceptin®-based therapy as determined by the objective response rate and/or the clinical benefit response rate (total of the number of responses and the number > 6 month stable diseases). |
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E.2.2 | Secondary objectives of the trial |
•To assess the safety profile of the combination of pertuzuamb and Herceptin®. •To determine the duration of response, time to response, time to progression, progression-free survival and overall survival. •To evaluate biomarkers that may be associated with clinical benefit due to pertuzumab in combination with Herceptin®.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed breast cancer. 2. HER2-positive tumors. HER2 status must be re-confirmed in a central lab before study entry. 3. Availability of a FFPE tumor tissue sample from primary tumor for eligibility (HER2-status) testing and biomarker assessment 4. Patients with metastatic breast cancer, who have progressed on Herceptin-based therapy as last treatment for metastatic disease. 5. Patients with ≤ 3 chemotherapy regimens prior to study entry. 6. The last dose of Herceptin must have been given ≤ 9 weeks prior to study day 1. 7. At least one measurable lesion according to RECIST. A measurable lesion in a previously irradiated area has to reveal clear signs of progression (increase in size of ≥ 50% or new lesions) 8. At least 4 weeks since prior radiotherapy, with full recovery. 9. At least 4 weeks since major surgery, with full recovery. 10. LVEF of ≥ 55 % or local parameter for ≥ LLN by echocardiography or MUGA. 11. Performance status ECOG ≤ 2. 12. Age ≥ 18 years 13. Signed informed consent. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with any targeted therapy other than Herceptin, such as cetuximab, bevacizumab, gefitinib or with anticancer vaccine. 2. Prior exposure to the following cumulative doses of anthracyclines: doxorubicin or liposomal doxorubicine > 360 mg/m2, epirubicin > 720 mg/m2, mitoxantrone > 120 mg/m2, idarubicin > 90 mg/m2 3. Known asymptomatic decreases in LVEF to below 50% absolute value during Herceptin treatment. 4. Patients with known history of any cardiac adverse event which according to the criteria of the investigator was related to Herceptin therapy. 5. History of congestive heart failure (any NYHA grading), unstable angina, evidence of transmural infarction on ECG, poorly controlled hypertension (systolic > 180 mm Hg and/or diastolic > 100 mm Hg), or hemodynamically significant valvular disease. 6. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma 7. Absolute Neutrophil Count (ANC) < 1.5 x 10(9)/L, Platelet count < 100 x 10(9)/L or Hb < 10 g/dL. 8. Impaired liver function: serum [total] bilirubin > 1.5 x ULN, AST, ALT > 2.5 x ULN, (> 5 x ULN in patients with liver metastases). 9. Serum creatinine > 2 x ULN 10. History or clinical evidence of brain metastases. 11. Severe uncontrolled systemic disease (e.g. hypertension, clinically significant cardiovascular, pulmonary, metabolic, wound-healing, ulcer, or bone fracture). 12. Patients with severe dyspnea at rest requiring supplementary oxygen therapy due to complications of advanced malignancy. 13. Positive serum pregnancy test in women of childbearing potential. 14. Patients with reproductive potential not willing to use effective method of contraception. 15. Pregnant or lactating women. 16. Patients with known infection with HIV, HBV, HCV. 17 Known hypersensitivity to Herceptin, murine proteins, or to any of its excipients. 18. Treatment with any investigational drug within 28 days prior to the start of the study. 19. Patients assessed by the investigators to be unable or unwilling to comply with the requirements of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response (OR): Objective response by tumor measurement according to RECIST criteria has occurred if there is documented and confirmed Complete Response (CR) or Partial Response (PR). Clinical Benefit Response (CBR): includes patients who have met the criteria for objective response at any time and for any duration (minimum of 4 weeks) and patients whose best response was stable disease (defined according to RECIST criteria) that lasted at least 6 months (or 8 cycles of therapy).
Both OR and CBR are based on evaluations of target and non-target lesions to ascertain the overall best response status of each patient.
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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 | Yes |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluation of biomarkers for clinical outcome |
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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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the study will be when all patients have died, or withdrawn consent or are lost to follow-up or when each patient has reached 3 years after the last study dose, whichever is earlier. However, the two stage study design allows an early termination of the study due to lack of efficacy or safety concerns. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |