Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer

NCT04088032 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 2019-00174 Neoadj Breast Pilot
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  The primary endpoints will be safety and tolerability of the study intervention

  Through study completion, up to 24 weeks

Secondary Outcomes (2)

• Pathologic response at surgery

  At the time of definitive surgery

• Pathologic response at surgery

  At the time of definitive surgery

Other Outcomes (4)

• Change in the number of T cells

  At the time of definitive surgery

• Change in the number of T regs cells

  At the time of definitive surgery

• Change in the number of macrophages

  At the time of definitive surgery

Study Arms (1)

Active

EXPERIMENTAL

Experimental treatment

Drug: Abemaciclib, durvalumab and aromatase inhibitor

Interventions

Abemaciclib, durvalumab and aromatase inhibitor DRUG

Subjects will receive standard therapy with an aromatase inhibitor (exemestane, anastrozole, or letrozole), combined with the experimental treatment of abemaciclib and durvalumab

Active

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \< 1.
• Patient must be able to swallow pills.
• Adequate organ and marrow function as defined below and in Table 1:
• Hemoglobin ≥ 9 g/deciliter
• Absolute neutrophil count ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 × institutional upper limit of normal (ULN)
• Bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 2 × ULN

You may not qualify if:

• 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.
• Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
• Major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of study drugs or still recovering from prior surgery
• Known history of tuberculosis
• Subjects who are known to be hepatitis B or C positive
• History of prior therapy with a checkpoint (PD-L1/PD-1) including durvalumab or CDK4/6 inhibitor

Sponsors & Collaborators

• Alison Stopeck: lead
• Eli Lilly and Company: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Stony Brook University Cancer Center

Stony Brook, New York, 11794, United States

Location

MeSH Terms

Interventions

abemaciclib; durvalumab; Aromatase Inhibitors

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Alison Stopeck, MD

  Stony Brook University

  STUDY DIRECTOR

• Lea Baer, MD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Division Chief Hematology/Oncology

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: September 12, 2019
• Study Start: October 1, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: July 16, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)