A study of abemaciclib combined with endocrine therapy (letrozole or fulvestrant)with or without a short course of chemotherapy with paclitaxel in patients withunresectable locally advanced or metastatic breast cancer with aggressive disease criteria.
- Conditions
- Previously untreated unresectable locally advanced or metastatic hormone receptor (HR)-positive/ human epidermal growth factor receptor 2 (HER2)-negative breast cancer with aggressive disease criteria.MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001648-24-IT
- Lead Sponsor
- MEDICA SCIENTIA INNOVATION RESEARCH S.L.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 160
1.Signed ICF prior participation in any study-related activities
2.Male/female patients#18y time signed ICF
3.ECOG performance status of 0/1
4.Life expectancy at least 24weeks
5.Pre-menopausal/peri-menopausal women who are being treated w/ a luteinizing hormone-releasing hormone analog for at least 28d prior to study entry(if shorter,post-menopausal levels of serum estradiol/follicle-stimulating hormone [FSH]must be confirmed analytically)/post-menopausal women as defined by any of following criteria:
a.Documented bilateral oophorectomy
b.Age#60y
c.Age<60y & cessation of regular menses for#12m consecutive w/ no alternative pathological/physiological cause;serum estradiol &/or FSH level within laboratory’s reference range for post-menopausal females
6.Unresectable locally advanced/MBC not amenable to resection w/ curative intent
7.At least 1of following aggressive disease criteria:
a.Presence of visceral disease
b.Either radiological as per RECIST v1.1 /Clinical evidence of progressive disease (PD)on /within 36m of completing adjuvant ET
c.High histological grade &/or PgR-negative status on primary tumor
d.LDH >1.5×ULN
8.Histologically confirmed ERs- &/or PGR(PgR)-positive & HER2-negative breast cancer based on local testing on the most recent analyzed biopsy
9.Measurable disease as per RECIST v1.1 w/ at least 1site of disease amenable to biopsy.Patients w/ bone lesions as only sites of metastatic disease are not eligible,except for patients w/ identifiable soft tissue components,evaluable by cross sectional imaging techniques such as CT /MRI,and that meet the definition of measurability according RECIST v1.1
10.Willingness & ability to provide tumor biopsy from metastatic site /primary breast tumor at time of inclusion to perform exploratory studies If not feasible,patient eligibility should be evaluated by Sponsor
11.Willingness to provide blood samples for exploratory studies at
baseline,after 2w treatment & at progression (or treatment termination prior to start alternative anti-cancer therapy)
12.Patients relapsing on a CDK 4/6 inhibitor-based regimen in the neoadjuvant /adjuvant setting will be suitable for the study if disease progression is confirmed after at least 12m following CDK4/6 treatment completion
13.No prior systemic therapy for unresectable locally advanced /metastatic disease
14.Radiation therapy for metastatic disease permitted,patient must have fully recovered from the acute effects & at least 14d must have elapsed b/w the last dose & randomization
15.Resolution of all acute toxic effects of prior anti-cancer therapy to
Grade#1 as determined by NCI-CTCAE v5.0 (except for Grade#2 neuropathy,alopecia,toxicities not considered a safety risk at investigator's discretion) within at least 14d prior to D1
16.Adequate hematologic & organ function within 14d before the 1st treatment on D1C1,defined by:
a.WBC>3.0×109/L;ANC#1.5×109/L(w/t GCSF support within 2w prior D1C1)Platelet count#100×109/L(w/t transfusion within 2w prior D1C1);Hemoglobin>9.0g/dL (w/t transfusion within 2w prior D1C1)
b.Serum albumin#3g/dL,Total bilirubin#1.5×ULN(#2×ULN in Gilbert’s disease)AST/ALT#3.0×ULN(in liver metastases #5×ULN)ALP#2.5×ULN(in liver and/or bone metastases #5×ULN)
c.Serum creatinine<1.5×ULN /creatinine clearance #30mL/min based on Cockcroft#Gault eGFR
d.PTT(or aPTT and INR#1.5×ULN
17.For women of childbearing potential:agreement to remain abstinent (refrain from heterosexual intercourse) /use highly effective contraceptive methods/
1. Known hypersensitivity to abemaciclib, letrozole, fulvestrant, paclitaxel, and/or any of their excipients.
2. Are currently receiving an investigational drug in a clinical study or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
Note: For patients who stopped receiving an investigational drug in another clinical study, a washout period of 21 days or 5- half-lives (whichever is shorter) must be observed before entering the trial.
3. Formal contraindication to ET defined as visceral crisis and rapidly or symptomatic progressive visceral disease.
4. Known concurrent malignancy or malignancy within 5 years of study enrollment except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the medical monitor is required.
5. Known active brain metastases and/or carcinomatous meningitis. Participants with previously treated brain
metastases may participate provided they are radiologically stable for =4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for =14 days prior to first dose of study treatment.
6. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
7. Major surgical procedure within 14 days prior to treatment initiation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis.
Note: Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.
8. Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed if used prophylactically).
9. Serious and/or uncontrolled pre-existing 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 <30 ml/min], history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn’s disease or ulcerative colitis or a pre-existing chronic condition resulting in baseline Grade 2 or higher diarrhea).
10. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
11. Active bacterial or fungal infection at the time of enrolment (requiring antibiotics or antifungal agents at time of initiating study treatment).
12. 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.
13. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit throug
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method