A Phase 2 trial using ARV-471 or Anastrozole in Post-Menopausal Women with Breast Cancer Prior to Surgery.
- Conditions
- Post-menopausal women with ER+ HER2– breast cancerMedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: PTClassification code 10083232Term: HER2 negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005081-17-DE
- Lead Sponsor
- Arvinas Estrogen Receptor, Inc. (Arvinas)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 150
Participants, for whom neoadjuvant endocrine monotherapy is deemed appropriate, are eligible to be included in the study only if all of the following criteria apply:
1. Post-menopausal females = 18 years
2. Histologically or cytologically confirmed ER+ and HER2– breast cancer (per local assessment)
3. Clinical T1c-T4c, N0-N2, M0 breast cancer amenable to definitive surgical resection, without bilateral breast ductal carcinoma in situ or invasive breast cancer
4. The primary tumor must be at least 1.5 cm by imaging
5. Willingness to undergo a screening biopsy, an on-treatment biopsy and surgical resection
6. Capable of giving signed informed consent
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Adequate bone marrow function
9. Activated partial thromboplastin time (aPTT) = 1.25 × upper limit of normal (ULN) and international normalized ratio (INR) = 1.25
10. Adequate renal function defined as serum creatinine of = 1.5 × ULN or an estimated creatinine clearance of = 50 mL/min by Cockcroft Gault
11. Adequate liver function
12. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1. Any other active malignancy within three years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or cervical carcinoma in situ.
2. Any of the following in the previous six months:
- Myocardial infarction
- Severe / unstable angina
- Coronary / peripheral artery bypass graft
- Symptomatic congestive heart failure (New York Heart Association class III or IV)
- Cerebrovascular accident
- Transient ischemic attack
- Symptomatic pulmonary embolism
3. Any of the following in the previous six months:
- Congenital long QT syndrome
- Torsade de Pointes
- Sustained ventricular tachyarrhythmia and ventricular fibrillation
- Left anterior hemiblock (bifascicular block)
- Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) = Grade 2
- Atrial fibrillation of any grade (= Grade 2 in the case of asymptomatic lone atrial fibrillation).
4. Active inflammatory gastrointestinal disease, chronic diarrhea, known uncontrolled diverticular disease, or previous gastric resection or lap band surgery
5. Cirrhosis meeting criteria for Child Pugh B and C
6. Major surgery (as defined by the Investigator) within four weeks of first dose of study drug
7. History of allergy or reaction to any of the drug components for ARV-471 or anastrozole, including patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
8. Inability to take oral medication without crushing, dissolving, or chewing tablets
9. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study
10. Prior treatment for breast cancer including systemic therapy (eg, chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents
11. Any live vaccines within 14 days of planned start of first dose of study drug
12. Taking the following agents within 14 days of C1D1 unless otherwise specified:
- Sensitive P-glycoprotein (P-gp) substrates or P-gp substrates with narrow therapeutic indices
- Strong CYP3A4 inhibitors or inducers
- Any medications with known QT risk, and/or are associated with a risk of Torsades de Pointes, within 7 days of C1D1
13. Corrected QT interval by Fredericia’s method (QTcF) > 470 msec
14. Participants with active, uncontrolled bacterial, fungal or viral infection, including (but not limited to) hepatitis B virus (HBV) and hepatitis C virus (HCV) and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
15. Participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Sponsor approval is required.)
16. Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
17. Investigator site staff or Sponsor employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the effects of ARV-471 and anastrozole, respectively, on Ki-67 expression in tumors after 2 weeks of treatment;Secondary Objective: 1. Evaluate the safety and tolerability of ARV-471 and anastrozole, respectively<br>2. Evaluate the clinical and pathological response of ARV-471 and anastrozole, respectively;Primary end point(s): Percent change in Ki-67 expression between baseline and Cycle 1 Day 15 tumor biopsies;Timepoint(s) of evaluation of this end point: Cycle 1 Day 15, i.e. after two weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Incidence of all adverse events, serious adverse events, and adverse events leading to study drug discontinuation<br>2. Pathologic stage, pathologic complete response (pCR) rate, and modified Pre-operative Endocrine Prognostic Index (mPEPI) score at the time of surgical resection (C6D18 ± 10 days); rates of breast conserving surgery; radiographic response of the primary tumor based on imaging during cycle 6; caliper-based response on C6D1;Timepoint(s) of evaluation of this end point: 1. During entire duration of the trial<br>2. At end of trial participation