E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 determine whether the combination of MM-121 + exemestane is more effective than exemestane alone based
on Progression Free Survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of the combination of MM-121 + exemestane to exemestane alone using :
- Overall survival
- Objective response rate and duration of response
- Clinical benefit rate
To determine the safety profile of the MM-121 + exemestane combination
To determine the immunogenicity parameters of the MM-121 + exemestane combination
To determine the pharmacokinetic parameters of the MM-121 + exemestane combination within a subset of
patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be included in the study, patients must have/be:
5.5.1. Progressed following treatment with prior anti-estrogen therapy in the locally advanced or metastatic setting, OR progressed during adjuvant treatment (or within 6 months following adjuvant treatment) with a non-steroidal aromatase inhibitor and/or tamoxifen
5.5.2. Histologically or cytologically confirmed ER+ and/or PR+ and Her2 negative breast cancer
5.5.3. Documented locally advanced or metastatic disease with at least one radiologically measurable lesion as defined by RECIST v1.1
Exception: patients with bone-only metastatic disease are eligible if they have at least 2 lesions on a bone scan or other imaging modality (e.g. X-Ray, CT, PET-CT or MRI) and have documented disease progression on prior therapy based on the appearance of new lesions
5.5.4. Able to understand and sign an informed consent (or have a legal representative who is able to do so)
5.5.5. Postmenopausal female patients, as defined by the following:
- 5 years since onset of menopause
- Luteinizing hormone/follicle-stimulating hormone levels in the postmenopausal range in women whose
menopause occurred less than 5 years before inclusion
5.5.6. Unstained tumor slides from tumor tissue available for analysis
5.5.7. ECOG Performance Score (PS) of ≤ 2
5.5.8. Adequate bone marrow reserves as evidenced by:
- ANC > 1,500/μl without the use of hematopoietic growth factors; and
- Platelet count > 100,000/μl; and
- Hemoglobin > 9 g/dL
5.5.9. Adequate hepatic function as evidenced by:
- Serum total bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline Phosphatase ≤ 2.5 x ULN (≤5 x ULN is acceptable if liver metastases are present; ≤ 5 x ULN of Alkaline Phosphatase is acceptable if bone
metastases are present)
5.5.10. Adequate renal function as evidenced by a serum creatinine ≤ 1.5 x ULN
5.5.11. Recovered from clinically significant effects of any prior surgery, radiotherapy or other antineoplastic
therapy. Patients with a known peripheral neuropathy must present as Grade 1 or less, according to National
Cancer Institute common terminology criteria [NCI CTCAE], version 4.0, to be eligible for inclusion.
5.5.12. 18 years or above of age |
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E.4 | Principal exclusion criteria |
Patients must meet all the inclusion criteria listed above and none of the following exclusion criteria:
5.6.1. Received prior treatment with exemestane
5.6.2. Received more than one prior chemotherapy regimen in the metastatic setting
5.6.3. Extensive visceral disease (rapidly progressive, life -threatening metastases, including symptomatic lymphangitic metastases)
5.6.4. Symptomatic CNS disease
5.6.5. History of another malignancy in the last 5 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone and have been continuously disease free for at least 5 years.
5.6.6. Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of
dosing, which in the investigator’s opinion might compromise the patient’s participation in the trial or affect the study outcome. At the discretion of the investigator, patients with tumor fever may be enrolled
5.6.7. Known hypersensitivity to any of the components of MM-121 or who have had hypersensitivity reactions to fully human monoclonal antibodies
5.6.8. Received other recent antitumor therapy including:
- Investigational therapy administered within the 30 days prior to the first scheduled day of dosing in this study
- Radiation or other standard hormonal therapy within 14 days prior to the first scheduled dose in this study,
including, in addition if necessary, the timeframe for any actual or anticipated toxicities from such radiation or
therapy
5.6.9. NYHA Class III or IV congestive heart failure or LVEF < 55%. Patients with a significant history of cardiac disease (i.e. uncontrolled blood pressure, unstable angina, myocardial infarction within 1 year or ventricular arrhythmias requiring medication) are also excluded
5.6.10. Recent (within 1 year) cerebral vascular accident (CVA)
5.6.11. History of allergic reactions attributed to compounds of similar chemical or biologic composition as exemestane
5.6.12. Planned bisphosphonate therapy which has not been initiated prior to randomization; bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy
5.6.13. Any other medical condition deemed by the Investigator to be likely to interfere with a patient’s ability to
sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
* To compare the efficacy of the combination of MM-121 + exemestane to exemestane alone using
* Overall survival
* Objective response rate and duration of response
* Clinical benefit rate
* To determine the safety profile of the MM-121 + exemestane combination
* To determine the immunogenicity parameters of the MM-121 + exemestane combination
* To determine the pharmacokinetic parameters of the MM-121 + exemestane combination within a subset of patients
|
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 |
Immunogenicity parameters of the MM-121 + exemestane combination |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 20 |
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 | No |
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 cut-off date for the study analysis will be when the last patient randomized reaches the 4 month evaluation visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |