Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer Female, Neoplasm, Breast, Breast Cancer Metastatic

Intervention / Treatment
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* Drug: Eribulin Injection [Halaven]
* Drug: Paclitaxel injection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eribulin<br>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]<br>* on days 1 and 8 q21d<br>* Other names: Eribulin;|
| Active Comparator: Paclitaxel<br>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<br>* on days 1, 8, and 15 q21d<br>* Other names: Paclitaxel;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoresponse