E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone Receptor Positive, HER2 negative Locoregionally Recurrent or Metastatic Breast Cancer with No Prior Systemic Therapy in This Disease Setting |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic 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 Study I3Y-MC-JPBM is to compare treatment with LY2835219 plus NSAI therapy versus placebo plus NSAI therapy with respect to PFS in postmenopausal women with HR+, HER2- locoregionally recurrent or metastatic breast cancer who have not received prior systemic therapy in this disease setting. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare the combination treatment of LY2835219 and NSAI therapy versus placebo plus NSAI therapy with respect to the following:
• OS
• OS rate at 1, 2, and 3 years;
• ORR (CR + PR);
• Duration of response (CR + PR);
• DCR (CR + PR + SD);
• CBR (CR + PR + SD ≥6 months);
• Safety and tolerability;
• Change in symptom burden from baseline using the EORTC QLQ-C30, EORTC QLQ-BR23 (breast) questionnaire, and health status scores from the EQ-5D 5L;
• PK of LY2835219, its metabolites, and NSAI therapy
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• have a diagnosis of HR+, HER2- breast cancer;
• have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease;
• have postmenopausal status due to either surgical/natural menopause or amenorrheic (non-treatment-induced) for at least 12 months;
• have either measurable disease or nonmeasurable bone-only disease as defined by RECIST v1.1;
• have a PS≤1 on the ECOG scale;
• have adequate organ function;
• have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization and recovered from the acute effects of therapy;
• are female and ≥18 years of age;
• are able to swallow capsules;
• have given written informed consent prior to any study-specific procedures
• are reliable, willing to be available for the duration of the study, and are willing to follow study procedures. |
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E.4 | Principal exclusion criteria |
• have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis. Visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
• have inflammatory breast cancer.
• have clinical evidence or a history of CNS metastasis. Screening is not required for enrollment.
• are currently receiving or have previously received endocrine therapy for locoregionally recurrent or metastatic breast cancer. [Note: A patient may be enrolled if she received prior (neo)adjuvant endocrine therapy (including , but not limited to anti-estrogens or aromatase inhibitors) for localized disease. In addition, a patient may be enrolled if she has received ≤2 weeks of NSAI in this disease setting immediately preceding screening and agrees to discontinue NSAI until study treatment initiation.]
• have received prior (neo)adjuvant endocrine therapy (e.g., anti-estrogens or aromatase inhibitors) with a disease-free interval ≤12 months from completion of treatment.
• are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer. [Note: Patients may be enrolled if they received prior (neo)adjuvant chemotherapy for localized disease.]
• have received prior treatment with everolimus
• have received prior treatment with any CDK4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)
• have initiated bisphosphonates or approved RANK ligand (RANK-L) targeted agents (for example, denosumab) <7 days prior to randomization
• are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and Lilly clinical research physician (CRP) is required to establish eligibility.
• have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively.
• have had major surgery within 14 days prior to randomization to allow for post-operative healing of the surgical wound and site(s).
• have received recent (within 28 days prior to randomization) yellow fever vaccination.
• have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis).
• have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
• have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
• have received an autologous or allogeneic stem-cell transplant.
• have active bacterial or fungal infection or detectable viral infection (for example, human immunodeficiency virus [HIV] or viral hepatitis). Screening is not required for enrollment. |
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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 |
Randomization up to investigator-determined objective progression or Death from Any Cause (Approximately 34 Months) |
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E.5.2 | Secondary end point(s) |
• Overall Survival (OS)
• Objective Response Rate (ORR)
• Duration of Response (DoR)
• Disease Control Rate (DCR):
• Clinical Benefit Rate (CBR)
• Safety and tolerability endpoints (e.g. physical examination, adverse event collection, lab tests, dosing information)
• Change in symptom burden using EORTC QLQ-C30, EORTC QLQ-BR23 questionnaire
• Change in health status using the EQ-5D 5L
• Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of LY2835219, its Metabolites, and NSAI Therapy:
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS: Baseline to approximately 82 Months
ORR, DoR, DCR, CBR, safety and tolerability endpoints (e.g. physical examination, adverse event collection, lab tests, dosing information change in symptom burden using the EORTC QLQ-C30, EORTC QLQ-BR23, change in health status using the EQ-5D 5L: Baseline to approximately 34 months
PK: Baseline up to approximately 4 months
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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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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 |
Australia |
Austria |
Belgium |
Canada |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
New Zealand |
Russian Federation |
Slovakia |
Spain |
Sweden |
Taiwan |
Turkey |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 | 6 |