Clinical trial NCT04796324: Anti-tumor Effect of Ixabepilone in Metastatic Breast Cancer (mBC) Selected by the Ixabepilone DRP.
Official title: Phase II, Open Label, Single Arm Study to Investigate Anti-tumor Effect of Ixabepilone in Patients With Locally Recurrent or Metastatic Breast Cancer (mBC) Selected by the Ixabepilone DRP After Failure of an Anthracycline and Taxanes.
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Allarity Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle.
Primary purpose: TREATMENT

Brief summary: The purpose is to investigate anti-tumor effect of ixabepilone in patients with locally recurrent or metastatic breast cancer (mBC) selected by the Ixabepilone DRP after failure of an anthracycline and taxanes.

Detailed description: Patients will be screened with the Ixabepilone DRP. If the tumor tissue has a DRP( Drug Response Prediction) score of \>67% (Belgium \>33%) the patient can be included in the clinical study. Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent form
2. Age 18 years or older
3. Patients with histologically or cytological confirmed carcinoma of the breast. Patients with locally recurrent or metastatic disease
4. Patients with HR-positive, HER negative tumors or triple negative tumors
5. Previous chemotherapies (neo, adjuvant or in the metastatic setting) must have included a taxane and an anthracycline unless anthracycline therapy is not indicated.
6. Maximum of three (3) prior chemotherapies in the metastatic setting in addition to any number of prior lines of endocrine therapy
7. Measurable disease
8. Performance status of ECOG ≤ 1
9. With an Ixabepilone DRP - score of \>33% (Germany \>67%)
10. Adequate conditions as evidenced by the following clinical laboratory values:

    1. Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
    2. Hemoglobin \> 6.2 mmol/L
    3. Platelets ≥ 100 x 109 /L
    4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
    5. Serum bilirubin ≤ 1.0 ULN
    6. Alkaline phosphatase ≤ 2.5 x ULN or ≤5x ULN if documented liver/bone metastases. Creatinine ≤ 1.5 ULN
    7. Blood urea within normal limits
11. Because of possible interference of cytochrome P450 3A4 activity by ixabepilone, patients were excluded from receiving the following medications at enrollment and while enrolled onto the study: amiodarone, clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole, indinavir, nelfinavir, ritonavir, and saquinavir
12. Women of childbearing age and potential must be willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential must be willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections)

Exclusion Criteria:

1. HER2 positive tumor
2. Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period
3. Patients with intracranial disease
4. Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study
5. Any active infection requiring parenteral or oral antibiotic treatment.
6. Patients with grade 2, in case of diabetes grade 1 or greater neuropathy
7. Clinically significant (i.e. active) cardiovascular disease:
8. Stroke within ≤ 6 months prior to day 1
9. Transient ischemic attach (TIA) within ≤ 6 months prior to day 1
10. Myocardial infarction within ≤ 6 months prior to day 1
11. Unstable angina
12. New York Hart Association (NYHA) Class II or greater congestive heart failure (CHF)
13. Serious cardiac arrhythmia requiring medication
14. Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation for safety reasons or interfere with the interpretation of study results.
15. Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy
16. Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry)
17. Known prior severe hypersensitivity reactions to agents containing polyoxyethylated castor oil (Cremophor EL)
18. Known hypersensitivity to fluoropyrimidines;
19. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency;
20. Patients must not continue treatment with the following strong inhibitors of CYP3A4:

ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole. These therapies should be discontinued 72 hours prior to initiation of study drug therapy.

Primary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: 1 year
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 1 year
measure: Overall response rate (ORR) defined as CR + PR
timeFrame: 1 year
measure: Incidence of Treatment-Emergent Adverse Events measured by NCI-CTCAE v.5.0
timeFrame: 1 year
measure: Clinical Benefit Rate (CBR) - fresh biopsy versus archival
timeFrame: 1 year
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
state: Edegem
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwziekenhuis
city: Brussels
country: Belgium
facility: Clin. Univ. Saint-Luc
city: Liege
country: Belgium
facility: CHU de Liege, Oncology Department
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Modena
country: Italy
facility: Modena University Hospital
city: Rotterdam
country: Netherlands
facility: Ikazia Hospital Rotterdam
city: Biala Podlaska
country: Poland
facility: Wojewodzki Szpital Specjalietyczny
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im.
city: Poznań
country: Poland
facility: Oddział Onkologii Klinicznej, Szpital Kliniczny Przemienienia Pańskiego UM w Poznaniu
city: Gillingham
country: United Kingdom
facility: Medway NHS Foundation Trust
state: Kent
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Taunton
country: United Kingdom
facility: Somerset NHS Foundation Trust
state: Somerset
city: Swansea
country: United Kingdom
facility: Cancer Institute Singleton Hospital
state: Wales
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre, Western General Hospital
city: Leeds
country: United Kingdom
facility: St James Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
Study officials:
References: