HER2 negative breastcancer HR+
Conditions
Interventions
Test Product, Dosage, and Mode of Administration: Abemaciclib will be supplied
as capsules administered
orally, 150 mg every 12 hours
Reference Therapy, Dose, and Mode of Administration: Anastrozole
Sponsors
Eli Lilly
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: [1] are female and >=18 years of age [2] have postmenopausal status, defined as meeting one of the following conditions: * prior bilateral oophorectomy * age >=60 years * age =1 cm in diameter, Stage II, or Stage IIIA or IIIB breast cancer (according to the AJCC Staging Manual, 7th Edition [Edge et al. 2010]). Multifocal disease is allowed if confined to 1 breast, and if each tumor is HR+, HER2- and at least 1 tumor is >=1 cm. [5] at least 1 measureable lesion according to RECIST criteria by physical examination or imaging tests [6] breast cancer that is HR+, HER2- * to fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least 1 of the hormone receptors (estrogen receptor [ER], progesterone receptor [PgR] as defined in the relevant American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] Guidelines [Hammond et al. 2010]) * to fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH), as defined in the relevant ASCO/CAP guidelines (Wolff et al. 2013) [7] neoadjuvant endocrine monotherapy is deemed to be a suitable therapy [8] primary breast cancer that is suitable for baseline core biopsy (provision of baseline core biopsy specimen is mandatory) [9] Eastern Cooperative Oncology Group (ECOG) performance status score =1.5 x 109/L, platelets >100 x 109/L, and hemoglobin >=8 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. However, initial study drug treatment must not begin earlier than the day of the erythrocyte transfusion. * hepatic: bilirubin
Exclusion criteria
Exclusion criteria: [14] are currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drugs used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study [15] bilateral invasive breast cancer [16] metastatic breast cancer (local spread to axillary or internal mammary lymph nodes is permitted) [17] inflammatory breast cancer, defined as the presence of erythema or induration involving one third or more of the breast [18] concurrent therapy with any other non-protocol anti-cancer therapy [19] history of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix [20] prior systemic therapy or radiotherapy for invasive or non-invasive breast cancer in the same breast as currently being treated [21] prior radiotherapy to the ipsilateral chest wall for any malignancy [22] prior anti-estrogen therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer. Prior hormone-replacement therapy is permitted. [23] concurrent treatment with postmenopausal hormone replacement therapy. Prior treatment must be stopped for at least 28 days prior to first baseline biopsy. [24] have received treatment with a drug that has not received regulatory approval for any indication within 14 days of randomization for a nonmyelosuppressive or 21 days of randomization for a myelosuppressive agent [25] have had major surgery within 14 days prior to randomization to allow for post-operative healing of the surgical wound and site(s) [26] have received recent (within 28 days prior to randomization) yellow fever vaccination [27] 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) [28] have 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 [29] have received an autologous or allogeneic stem-cell transplant [30] 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. [31] male subjects [32] known hypersensitivity to loperamide hydrochloride or to any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of Study I3Y-MC-JPBY (JPBY) is to compare the biological activity of abemaciclib in combination with anastrozole, abemaciclib monotherapy, and anastrozole monotherapy by assessing the percentage change from the baseline value in Ki67 expression after 2 weeks of therapy. Efficacy: * percent change in Ki67 expression from baseline to the core biopsy 2 weeks after the start of treatment * pCR defined as absence of invasive cancer in the breast and sampled regional lymph nodes * clinical response of the breast tumor to therapy as assessed by caliper measurement * radiologic response of the breast tumor as assessed by radiologic or ultrasound assessment Safety: * adverse events Health Outcomes: * EORTC QLQ-C30 Pharmacokinetics: * PK of abemaciclib and its metabolites and anastrozole Pharmacodynamics: * Ki67 Biomarkers: * Whole blood, plasma, and tissue samples will be tested for biomarkers relevant to abemaciclib and the disease state and to correlate these markers to clinical outcomes. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives of the study are to evaluate after 14 additional weeks of neoadjuvant therapy: -pathologic complete response defined as absence of invasive cancer in the breast and sampled regional lymph nodes -clinical objective response (Response Evaluation Criteria in Solid Tumors [RECIST] criteria 1.1) -radiologic response (RECIST criteria 1.1) -safety and tolerability -symptom burden via the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) instrument -pharmacokinetics of abemaciclib and anastrozole. Exploratory Objectives -to assess the association between biomarkers and biological, pathological, and clinical outcome(s) -to evaluate the relationship between abemaciclib exposure and response variables, such as Ki67, change in tumor size, and clinical response | — |
Countries
Netherlands
Outcome results
None listed