E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Estrogen Receptor Positive 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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 compare the combination treatment of everolimus and exemestane to exemestane alone with respect to progression-free survival in postmenopausal women with estrogen receptor positive breast cancer refractory to NSAIs. |
|
E.2.2 | Secondary objectives of the trial |
Key Secondary Objective
▪To compare overall survival (OS) between the 2 treatment armsOther Secondary Objectives
▪To evaluate the two treatment arms with respect to ▫Overall response rate (ORR) ▫Time to deterioration of ECOG Performance Status ▫Safety ▫Change in QoL scores over time ▫Clinical benefit rate (CBR
▪Both everolimus and exemestane are substrates of CYP3A4 and there is a
potential DDI between the two drugs. The study will therefore,
▫characterize, in a subgroup of patients, the pharmacokinetics of everolimus
(Cmin, C2h) when administered in combination with exemestane.
▫compare the two treatment arms with respect to pre-dose concentration (Cmin)
and concentration at 2 hours post dose (C2h) of exemestane and to compare, in
a subgroup of patients, the two treatment arms with respect to estradiol (E2)
changes from baseline. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
•Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
•Postmenopausal women.
•Disease refractory to non steroidal aromatase inhibitors (NSAI),
•Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
•Patients must have at least one lesion that can be accurately measuredor bone lesions in the absence of measurable disease
•Adequate bone marrow and coagulation function
•Adequate liver and renal function
•ECOG Performance Status = 2 or lessOther protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
• HER2-overexpressing patients
•Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
•Patients who received more than one chemotherapy line for Advanced Breast Cancer.
•Previous treatment with exemestane or mTOR inhibitors.
•Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
•Radiotherapy within four weeks prior to randomization
•Currently receiving hormone replacement therapy,
•Patients receiving immunosuppressive agents or chronic corticosteroids use
•Patients being treated with strong inhibitors or inducers of CYP3A within 5 days prior to randomization
Other protocol-defined exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
progression-free survival (PFS), defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 | 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
|
The End of Study visit is the date when no further patient information will be collected, including reasons for death or lost to follow-up. It occurs after the last survival information is collected. |
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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 | |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 3 |