Low-Estrogen Receptor (ER) positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative Early Breast Cancer (BC) MedDRA version: 23.0 Level: PT Classification code 10083232 Term: HER2 negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Abemaciclib
Product Code: [LY2835219]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Abemaciclib
CAS Number: 1231929-97-7
Current Sponsor code: LY2835219
Other descriptive
Sponsors
GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adult patients, male or female aged = o > 18 years at the time of informed consent. • T1cN0 - T3N0 infiltrating breast cancer without evidence of metastatic disease, not previously treated. • Histologically confirmed diagnosis of infiltrating breast cancer with low estrogen receptor positivity (1-10%). • HER2-negative breast cancer defined with a negative in situ hybridization test (ISH) or an immunohistochemical status (IHC) of 0, 1+, or 2+. If IHC is 2+, a negative in situ hybridization test (FISH, CISH or SISH) is required • Ki67 at the diagnostic biopsy, assessed by the local laboratory, with a value> 15% • Patients must have clinically and / or radiographically documented measurable disease according to RECIST 1.1 criteria. • All radiological examinations must be performed within 28 days prior to registration (35 days if negative). • Availability, at the time of registration, of a tumor sample of the primary tumor lesion fixed in formalin and embedded in paraffin (FFPE). • Previous (neo) adjuvant anticancer therapy is not allowed. • The patient must have an ECOG (Eastern Cooperative Oncology Group) performance status 1.5 × ULN. • Patients with respiratory insufficiency cannot be enrolled. If clinically indicated, lung function tests including measurements of predicted lung volumes, DLco, and resting ambient air oxygen saturation should be considered to rule out restrictive lung disease, pneumonia, or pulmonary infiltrates. • The patient should not have a known history of HIV infection (testing not mandatory). • Patients should not have a known history of hepatitis B or C (testing not mandatory). • Serum creatinine 50 ml / min according to the Cockcroft-Gault formula. • Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected within normal limits with supplements before the first dose of study drug. • INR < o = 1.5. • The patient must not have other serious and / or uncontrolled concomitant medical conditions which, in the investigator's judgment, could cause unacceptable safety risks, contraindicate patient participation in the clinical trial, or compromise protocol compliance (eg. Chronic pancreatitis, chronic active hepatitis, untreated or uncontrolled active fungal, bacterial or viral infections, etc.). • Patients should not have any clinically significant, uncontrolled heart disease and / or cardiac repolarization abnormalities. Please refer to the protocol For the full list of inclusion criteria. Are the trial subjects unde
Exclusion criteria
Exclusion criteria: • Patient has been diagnosed with locally advanced or stage IV BC. • Ki67 expression in core biopsy specimen < o = 15% as evaluated by local laboratory. • Patient has been treated with Abemaciclib. • Patient has been treated with any other investigational agent or has participated in another clinical trial within 28 days prior to enrolment. • Patient has received breast radiotherapy prior to registration. • Patient has a known hypersensitivity to any of the excipients of Abemaciclib. • The patient has any disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications. • The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea). • The patient has any uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. • The patient has active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment. • The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. • Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer. • Females who are pregnant or lactating. • Patient of childbearing / reproductive potential do not want to use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. • Patient with unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antiproliferative effect of Abemaciclib in the neoadjuvant phase in terms of change in Ki67 values found before and after treatment in patients with low positivity for ER/HER2 negative.;Secondary Objective: To evaluate the clinical activity of neoadjuvant therapy with Abemaciclib in terms of objective response rate (ORR) in patients with low positive ER / HER2 negative breast cancer. To assess the safety, feasibility, and survival outcomes of the study treatment. To evaluate the role of the tumor phenotype, determined by standard immunohistochemical approaches (IHC) and / or by the gene expression profile (GEP), in predicting the antiproliferative effect and clinical outcome of the study treatment. To explore the correlation of PI3CA / ESR1 / FGFR / p16 / CYCLIND mutations, RB and BRCA1 / 2 status with clinical outcome. To evaluate immune biomarkers that may be related to changes in the host's immune response and clinical outcome. To evaluate the role of organoid co-culture with autologous TIL in predicting response to the study regimen. (see protocol for space limit);Primary end point(s): Change in KI67 measured at baseline and at the end of treatment with Abemaciclib.;Timepoint(s) of evaluation of this end point: The study will be carried out according to Optimal Simon’s two stage design. The first stage ends after 10 patients have been evaluated, and if none of them exhibited an objective response, the study will be terminated. Otherwise, enrolment will continue until a sample size of 29 individuals has been reached. If at least 4 objective responses will be observed by the end of stage two, then the study treatment will be considered successful. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical endpoints: • Objective response rate (ORR), defined as the proportion of participants who have a complete response (CR) or partial response (PR), as determined by the local investigator using RECIST 1.1 criteria. • Toxicity (both predefined and not predefined side effects will be recorded, classified, graded and managed according to NCI Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). • Disease-free survival (DFS), defined as the date of diagnosis of primary breast cancer to the date of local, regional, or distant invasive recurrence or death of any cause.; Translational endpoints: • Association of Ki-67 expression with ORR and DFS. The analysis will include evaluation of tumor samples at baseline and at the end of treatment for Ki-67 expression by IHC. • Association of HER2 status with Ki-67 variation, ORR and DFS. The analysis will include assessment of tumor samples at baseline and at the end of treatment for HER2 expression by IHC. • Association of GEP with variation of Ki-67, ORR and DFS. The analysis will include evaluation of tumor samples at baseline and at the end of treatment for GEP using PAM50 nanostring. • Association of TILs with Ki-67 variation, ORR and DFS. The analysis will include evaluation of basal and end-of-treatment tumor samples for TILs (sections stained with hematoxylin and eosin (H-E) and IHC [immunophenotype]). • Association of PI3CA, ESR1, FGFR, p16, CYCLIND, RB and BRCA1 / 2 mutations with variation of Ki-67, ORR and DFS. The analysis will include assessment of baseline and end-of-treatment samples for gene mutations (PI3CA / ESR1 / FGFR / p16 / CYCLIND / RB / BRCA). • Association of expression of PI3CA, ESR1, FGFR, p16, CYCLIND, RB and BRCA1 / 2 mRNA with variation of Ki-67, ORR and DFS. Analysis will include assessment of tumor samples at baseline and at the end of treatment for PI3CA / ESR1 / FGFR / p16 / CYCLIND / RB / BRCA mRNA expression. • Association of the expression of PI3CA | — |
Countries
Italy
Contacts
Public ContactOncologia Azienda Ospedaliero Unive
Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)
Outcome results
None listed