A Pilot Neoadjuvant Clinical Trial of Combination Therapy With Abemaciclib, Durvalumab (MEDI4736), and an Aromatase Inhibitor in Locally Advanced Hormone Receptor Positive Breast Cancer

Alison Stopeck1 site in 1 countryOctober 1, 2019

ConditionsBreast Cancer Female Locally Advanced Breast Cancer Hormone Receptor Positive Malignant Neoplasm of Breast

InterventionsAbemaciclib, durvalumab and aromatase inhibitor

DrugsAbemaciclib, durvalumab and aromatase inhibitor

Overview

Phase: Early Phase 1
Intervention: Abemaciclib, durvalumab and aromatase inhibitor
Conditions: Breast Cancer Female
Sponsor: Alison Stopeck
Locations: 1
Primary Endpoint: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Status: Withdrawn
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to test the efficacy, safety and tolerability of a combination of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive breast cancer.

Detailed Description

The primary hypothesis is that a Programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor combined with a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor will be well tolerated in early stage, hormone receptor positive (HR+) breast cancer patients treated with neoadjuvant endocrine therapy (NET). The secondary hypothesis and biomarker based endpoint is that patients with HR positive locally advanced breast cancer with low to intermediate stromal tumor-infiltrating lymphocytes (TILs) will demonstrate an increase in stromal TILs following NET when combined with abemaciclib and durvalumab for 4 cycles (16 weeks).

Registry

clinicaltrials.gov

Start Date

October 1, 2019

End Date

December 31, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Alison Stopeck

Responsible Party

Sponsor Investigator

Principal Investigator

Alison Stopeck

Division Chief Hematology/Oncology

Stony Brook University

Eligibility Criteria

Inclusion Criteria

•A signed, written informed consent will be obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
•Postmenopausal women age ≥ 18 years at time of study entry. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
•Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
•Women \<50 years of age receiving luteinising hormone-releasing hormone (LHRH) agonist for ovarian suppression are also eligible for the study but must initiate LHRH agonist therapy at least 2 weeks prior to starting on study intervention.
•Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
•Histologically confirmed estrogen and/or progesterone positive invasive breast cancer, defined as either estrogen and/or progesterone receptor (ER/PR) staining \>10%, AND Human Epidermal Growth Factor Receptor 2 (HER2) negative by either Immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH).
•Clinical stage II-III disease with no clinical or radiologic evidence of metastatic disease. Patients must have a measurable primary breast lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
•Eastern Cooperative Oncology Group (ECOG) status \<
•Patient must be able to swallow pills.
•Adequate organ and marrow function as defined below and in Table 1:

Exclusion Criteria

•Any serious preexisting medical condition(s) that would place the patient at increased risk for toxicities including interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel.
•Body weight \< 30 kg (or 66.5 lbs.). If during the study, the patient's weight drops to \< 30 Kg (or 66.5 lbs), they will be withdrawn from the study.
•Females who are pregnant or lactating.
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
•Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible
•History of significant cardiac disease including heart failure, ventricular arrhythmia, or prolonged QT syndrome.
•Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline ≥ Grade 2 diarrhea.)
•History of primary immunodeficiency, or subjects who are known to be HIV (Human Immunodeficiency Virus ) positive
•History of organ transplant that requires use of immunosuppressives
•Known allergy or reaction to any of the study drugs.