Clinical trial NCT05033769: Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
Official title: AIRE - Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer - a Prospectively Randomized Phase IV Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Breast Cancer Female
Neoplasm, Breast
Breast Cancer Metastatic
Keywords: Immunoresponse
Lead sponsor: Institut fuer Frauengesundheit
Sponsor class: OTHER
Collaborators: name: Eisai GmbH
First posted: 2021-09-05
Enrollment: 82
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Immune responsivity (IR)
timeFrame: 12 weeks after therapy start
Secondary outcomes:
measure: Overall response after three months
timeFrame: three months after therapy start
measure: Progression free survival
timeFrame: 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
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months
measure: Toxicity and safety of eribulin and paclitaxel
timeFrame: Therapy start until 30 days post last dose
measure: EORTC QLQC30
timeFrame: Therapy start until therapy end after 4 cycles up to 12 weeks
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: Department of Gynecology, Tübingen University Hospital
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Department of Gynecology and Obstetrics, Erlangen University Hospital
state: Bavaria
Study officials:
affiliation: Department of Gynecology and Obstetrics, Erlangen University Hospital
name: Peter A Fasching, MD, Prof.
role: STUDY_CHAIR
References: