E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic 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 | 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 |
The overall objectives of this study are to compare the efficacy, safety and tolerability of AS1402 in combination with letrozole to letrozole alone as first-line treatment in post menopausal women with locally advanced or metastatic breast cancer. The primary objective is to compare the overall tumour response rate per RECIST in postmenopausal women with metastatic or locally advanced advanced breast cancer receiving AS1402 in combination with letrozole compared to letrozole alone |
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E.2.2 | Secondary objectives of the trial |
• To compare the progression-free survival (PFS) of patients receiving AS1402 in combination with letrozole compared to letrozole alone • To compare the time to progression (TTP) of patients receiving AS1402 in combination with letrozole compared to letrozole alone To compare the duration of response and stable disease (per RECIST) of patients receiving AS1402 in combination with letrozole compared to letrozole alone • To compare the clinical benefit rate (CBR = PR+CR+(SD >24 weeks)) of patients receiving AS1402 in combination with letrozole compared to letrozole alone • To compare the safety in postmenopausal women with metastatic or locally advanced breast cancer receiving AS1402 in combination with letrozole compared to letrozole alone
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For enrolment into the study, patients must satisfy the following criteria: 1. Willing and able to provide written informed consent and in the opinion of the Investigator be able to comply with the study assessments and follow-up 2. Histologically or cytologically confirmed locally advanced or metastatic breast cancer not amenable to curative therapy 3. Measurable disease according to the RECIST criteria 4. Estrogen receptor-positive and/or progesterone receptor-positive tumour 5. Postmenopausal women defined as a. Natural menopause with last menses more than 1 year ago, or b. Radiotherapy-induced menopause with last menses more than 1 year ago, or c. Chemotherapy-induced menopause with last menses more than 1 year ago AND serum follicle-stimulating hormone and luteinizing hormone and estradiol levels clearly in the postmenopausal range, or d. Bilateral oophorectomy 6. Performance status 0 or 1 7. Granulocyte count > 1.0 x 10^9/l 8. Platelet count > 100 x 10^9/l 9. Bilirubin < 2 times the upper limit of normal (ULN) 10. AST and/or ALT < 5 times ULN 11. Creatinine Clearance > 30 ml/min. |
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E.4 | Principal exclusion criteria |
Patients with any of the following will be excluded from the study: 1. Prior chemotherapy and/or endocrine therapy for advanced breast disease 2. Relapse within 12 months after treatment discontinuation of an aromatase inhibitor in the adjuvant setting 3. Unknown hormonal receptor status 4. Known HER2/neu-positivity defined by either a. 3+ by immunohistochemistry, or b. HER2-positive by fluorescent in situ hybridization 5. Pregnant or nursing 6. Known HIV positivity 7. Ongoing or active infection (grade >1) 8. Psychiatric illness or social situation that would preclude study compliance 9. Other uncontrolled illness 10. History of other malignancy within the last 5 years, not including curatively treated carcinoma in situ of the cervix or non-melanoma skin cancer. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: The primary efficacy endpoint is overall response rate (ORR).
Secondary endpoints: - Progression-free survival (PFS) - Time to progression (TTP) - Duration of overall response and duration of stable disease - Clinical benefit rate (CBR) - Safety and tolerability of AS1402 when combined with letrozole |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5.1 | Number of sites anticipated in the EEA | 7 |
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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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |