Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer (AIRE)

AIRE - Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer - a Prospectively Randomized Phase IV Study

After progression of disease after one chemotherapy, metastatic breast cancer patients will be randomized 1:1 to one of the following treatment arms:

Arm A. Eribulin Arm B. Paclitaxel

Blood draws for immune analysis will be performed before start of therapy, on day 1 of cycle 2 and on day 21 of cycle 4 (end of therapy) for the primary study aim. Patients will be treated under study conditions for a maximum of 4 therapy cycles.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Female; Breast Cancer Metastatic; Neoplasm, Breast
• Intervention / Treatment: Drug: Eribulin Injection [Halaven]; Drug: Paclitaxel injection

Detailed Description

This is a prospective, randomized Phase IV study. Patients who progressed after one chemotherapy in the metastatic setting will be randomized 1:1 to one of the following treatment arms. Arm A. Eribulin 1.23 mg/m2 on days 1 and 8 q21d Arm B. Paclitaxel 80 mg/m2 on days 1, 8, and 15 q21d Blood draws for immune analysis will be performed before start of therapy on day 1 of cycle 1, on day 1 of cycle 2 (pre dose each) and on day 21 of cycle 4 (end of therapy) and assessed for the primary study aim. Patients will be treated under study conditions for a maximum of 4 therapy cycles.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: AIRE Study manager; Phone Number: +49 (0) 9131 927 9578; Email: aire@ifg-erlangen.de

Study Locations

• Germany
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • Department of Gynecology, Tübingen University Hospital
      • Contact: Andreas Hartkopf, MD, Prof.; Phone Number: +49 07071 29 82211; Email: andreas.hartkopf@med.uni-tuebingen.de
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Department of Gynecology and Obstetrics, Erlangen University Hospital
      • Contact: Peter A Fasching, Prof. Dr.; Phone Number: 43470 +49 9131 85; Email: peter.fasching@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent prior to beginning of trial specific procedures
• Subject must be female and aged ≥ 18 years on day of signing informed consent
• ECOG 0-1
• Histologically confirmed, HER2 negative breast cancer determined by core biopsy of tumor lesion. Human epidermal growth factor receptor 2 (HER2) negativity is defined as either of the following by local laboratory assessment: In situ hybridization (ISH) non-amplified (ratio ≤ 2.2), or IHC 0 or IHC 1+.
• Indication for chemotherapy
• Previous therapy with one chemotherapy line
• Target lesion (RECIST 1.1)
• Adequate organ function defined as:

Creatinine Clearance > 50 ml/min ANC ≥ 1.5 x 10 3 /μL Thrombocytes > 100 x 10 3 /μL

Exclusion Criteria:

• HER2 positive disease
• Indication for an anti-hormone treatment
• Active infection requiring systemic therapy.
• Active autoimmune disease or other diseases that requires systemic treatment with corticosteroids or immunosuppressive drugs.
• History of primary or acquired immunodeficiency (including allogenic organ transplant).
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• Severely impaired liver function (Child Pugh C)
• Hypersensitivity to study medication or any of its components
• Neuropathy (PNP) > Grade 2 (CTCAE 5.0)
• Congenital long QT syndrome
• Preexisting concomitant use of strong CYP3A4 and CYP2C8 inhibiting or inducing drugs
• Life expectancy of less than three months
• Pregnancy (contraception is required according tocontraceptive guidance)
• Lactation
• Known history of following infections: Human immunodeficiency virus (HIV), History of acute or chronic Hepatitis B or Hepatitis C
• Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
• Does not agree to blood collection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eribulin; Arm A. Eribulin 1.23 mg/m^2, administered as an injection on day 1 and 8 q 21d for a maximum of 4 therapy cycles	Drug: Eribulin Injection [Halaven]; on days 1 and 8 q21d; Other Names: Eribulin
Active Comparator: Paclitaxel; Paclitaxel 80 mg/m^2, administered as an injection on day 1, 8 and 15 q21d for a maximum of 4 therapy cycles	Drug: Paclitaxel injection; on days 1, 8, and 15 q21d; Other Names: Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune responsivity (IR)	defined as ≥ 5% of all T cells from peripheral blood are Ki-67 positive after chemotherapy	12 weeks after therapy start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response after three months	Overall response	three months after therapy start
Progression free survival	Progression free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall survival	Overall survival	From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months
Toxicity and safety of eribulin and paclitaxel	Toxicity and safety of eribulin and paclitaxel	Therapy start until 30 days post last dose
EORTC QLQC30	Quality of life assessed via EORTC QLQC30	Therapy start until therapy end after 4 cycles up to 12 weeks

Collaborators and Investigators

• Sponsor: Institut fuer Frauengesundheit
• Collaborators: Eisai GmbH
• Investigators: Study Chair: Peter A Fasching, MD, Prof., Department of Gynecology and Obstetrics, Erlangen University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): September 15, 2023

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Immunoresponse
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: IFG-06-2019; 2020-001938-35 (EudraCT Number); AGO-B-049 (Other Identifier: AGO-B-ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No