E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ER positive, high proliferation breast |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 primary objective of the study is to evaluate the progression free survival (PFS) for the triplet combination of ridaforolimus, dalotuzumab and exemestane (R/D/E) compared to the combination of ridaforolimus and exemestane (R/E) in post-menopausal patients with high proliferation, estrogen receptor positive breast cancer that have progressed following treatment with a non-steroidal aromatase inhibitor. |
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E.2.2 | Secondary objectives of the trial |
): In post-menopausal patients with high proliferation, estrogen receptor positive breast cancer who have progressed following treatment with a non-steroidal aromatase inhibitor, the secondary objectives of this trial are the following:
• To evaluate the effectiveness of the triplet combination of ridaforolimus, exemestane and dalotuzumab (R/D/E) compared to ridaforolimus and exemestane (R/E) with respect to percent (%) reduction from baseline in the sum of imaging measurements (target lesion line lengths or volumetric images) at 16 weeks.
• To evaluate the objective response rate, as measured by RECIST 1.1 of the triplet combination of R/D/E compared to the combination of R/E.
• To estimate the overall survival for the triplet combination of R/D/E compared to the combination of R/E.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Metastatic, ER positive, HER2 negative Breast Cancer
2. High Proliferative (as measured by a Ki67 labeling index >15%)
3. Post menopausal
4. Previous treatment with either letrozole or anastrozole
5. AT least 1 measurable lesion
6. At least 18 years of age
7. Greater than or equal to 1 on the ECOG performance status.
8. Life expectance greater than 3 months
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E.4 | Principal exclusion criteria |
1. Patient is on other therapy for their cancer (Bisphosphonates and denosumab for the treatment of bone metastases are allowed, if they were initiated at least 28 days prior to randomization.)
2. Patient is in another study or is receiving an experimental agent.
3. Patient has previously received rapamycin or rapamycin analogs, including ridaforolimus, temsirolimus, or everolimus.
4. Patient has received prior treatment with IGF-1R inhibitors, PI3K inhibitors, or other experimental agents that target PI3K, AKT, or mTOR pathway
5. Patient who has had chemotherapy, radiotherapy, or biological therapy within 4 weeks [(6 weeks for nitrosoureas, mitomycin C, or bevacizumab and 2 weeks for hormonal therapy and kinase inhibitors)] prior to entering the study or who has not recovered from adverse events from prior treatment to at least grade 1 or baseline.
6. Patient has active brain metastasis or leptomeningeal carcinomatosis;
7. Patient has poorly controlled Type 1 or 2 diabetes, defined as a hemoglobin A1C greater than 8% or a fasting glucose of > 160 mg/dL.
8. Patient is known to be HIV positive.
9. Patient has a known history of active Hepatitis B or C. Patients who are seropositive for Hepatitis B surface antibody as their only evidence of prior hepatitis exposure are allowed.
10. Patient has a requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A). Patients should be off these medications for at least 2 weeks prior to the first dose of ridaforolimus. Concomitant medications that are metabolized by CYP3A are allowed (e.g., simvastatin or atorvastatin). See Appendix 6.1 for examples of CYP3A inducers and inhibitors.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression Free Survival according to RECIST 1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 8 calendar weeks while on treatment |
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E.5.2 | Secondary end point(s) |
1. Percent (%) change from baseline in the sum of target lesions by linear CT analysis at 16 weeks.
2. Percent (%) change from baseline in the sum of target lesions by tumor volume analysis at 16 weeks
3. Objective response rate, as measured by RECIST 1.1.
4. Overall survival will be assessed every 3 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
: 16 weeks for endpoints 1 and 2. Every 8 weeks for objective 3 every three months after disease progression. |
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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 | 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) | 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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Brazil |
Canada |
Colombia |
Israel |
Korea, Democratic People's Republic of |
Peru |
Taiwan |
United States |
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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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LVLS or; SPONSOR has right to terminate the study at any time. Reasons may include: quality or quantity of data recording is inaccurate or incomplete; poor adherence to protocol and regulatory requirements; the incidence or severity of adverse drug reaction in this or other studies indicates a potential health hazard to patients; plans to modify or discontinue the development of the study drug; or if study drug(s) is approved for marketing and available commercially. See protocol. |
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |