E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment in patients with advanced, HER2-positive breast cancer |
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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 | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
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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 |
•Feasibility Part:To evaluate the safety and tolerability profile of the combination docetaxel at a dose of 75mg/m2 i.v. q3w with TDM1 (explored at an initial dose of 2.4 mg/kg and escalated to 3.6mg/kg i.v. q3w) in patients with HER2 +, inoperable, locally advanced or mBC. •Extended Part:2nd+ line patients: To validate the feasibility of the recommended TDM1 dose in combination with docetaxel q3w. 1st line patients: to explore if docetaxel can be escalated to 100mg/m2 from the 2nd cycle onwards in patients without major toxicity in the 1st cycle. •Further Feasibility:Upon approval of a protocol amendment providing details of the feasibility of T-DM1–pertuzumab combination data (results of TDM4373g/BO22495), it is intended to add an additional cohort of 3-6 patients with T-DM1-docetaxel-pertuzumab combination (with T-DM1-docetaxel as obtained by the currently proposed study). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the: • Toxicity profile • Progression Free Survival (PFS). • Overall Response Rate (ORR). • Clinical Benefit Rate (CR, PR or SD for at least 6 months). • Duration of Response (DR). • Time to treatment failure (TTF). • Overall Survival (OS). • Pharmacokinetic (PK) characteristics of T-DM1 when combined with docetaxel. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- HAHA assessment - PK assessment - RCR specimens: tumor samples, tumor biopsies, blood/serum samples
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E.3 | Principal inclusion criteria |
1. Signed written informed consent. 2. Age ≥ 18 years. 3. ECOG PS of 0 or 1. 4. Life expectancy of ≥ 12 weeks. 5. Histologically or cytologically confirmed breast cancer, which is documented to be inoperable, locally advanced, or metastatic, amenable for treatment with docetaxel. 6. Evaluable or measurable disease (as defined by RECIST 1.0). 7. HER2-positive disease locally confirmed by HER2 protein over expression. 8. History of progression within 3 months prior to study entry |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating females. 2. Women of childbearing potential unless surgically sterile or using adequate measures of contraception (intra-uterine device or barrier method of contraception in conjunction with spermicidal jelly). 3. Patients must not have received radiotherapy for the treatment of metastatic or locally recurrent/advanced disease other than for the relief of the pain in progressing metastatic bone lesions (limited to < 30% of marrow bearing bone) and/or brain metastasis. 4. Significant cardiac disease including but not confined to: - Inadequate left ventricular ejection function (LVEF) at baseline, as defined as LVEF ≤50% by either echocardiogram or MUGA. - New York Health Association (NYHA) Class ≥I congestive heart failure. - Current unstable angina or serious cardiac arrhythmia despite adequate medication. - Myocardial infarction or clinically significant valvular heart disease within the last 6 months prior to enrollment in the study. - History of exposure to high doses of anthracyclines. 5. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability, which could affect ability to give informed consent, or compliance with study drugs. 6. Brain metastases that are untreated, symptomatic or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastasis within 2 months of the first study treatment. CT or MRI scan of the brain is mandatory within 28 days of first treatment. 7. Treatment with any investigational drug within 30 days prior to commencing treatment with study drug. 8. Inadequate organ function of the. a) Liver. b) Kidney. c) Bone marrow. d) Peripheral nervous system:Peripheral neuropathy of ≥Grade 2 per NCI CTC for AE Version 3.0. 9. Patients with serious, uncontrolled, intercurrent illness including infections (bacterial or viral) and poorly controlled diabetes mellitus. 10. Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen. 11. Incomplete wound healing following major surgical procedure, open biopsy or significant traumatic injury or anticipation of the need for major surgery during the course of the study treatment. 12. Known hypersensitivity to any of the study drugs, trastuzumab, murine proteins or excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
feasibility of the combination of docetaxel and TDM1 |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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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The end of the study is defined as the date of the last visit of the last patient participating in this trial. The last visit is defined as the safety follow up visit for the last patient. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |