Anti-tumor Effect of Ixabepilone in Metastatic Breast Cancer (mBC) Selected by the Ixabepilone DRP.

Metastatic Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04796324
• Other study ID #: AL-2001
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2021
• Est. completion date: November 1, 2025

Study information

• Verified date: November 2023
• Source: Allarity Therapeutics
• Contact: Joëlle COLLIGNON, Dr.
• Phone: 3242844343
• Email: veronique.loo[@]chuliege.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: November 1, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Ixabepilone Injection
Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle

Locations

Country	Name	City	State
Belgium	Onze-Lieve-Vrouwziekenhuis	Aalst
Belgium	Antwerp University Hospital	Antwerp	Edegem
Belgium	Clin. Univ. Saint-Luc	Brussels
Belgium	CHU de Liege, Oncology Department	Liege
Finland	Tampere University Hospital	Tampere
Germany	Charité - Universitätsmedizin Berlin	Berlin
Italy	Modena University Hospital	Modena
Netherlands	Ikazia Hospital Rotterdam	Rotterdam
Poland	Wojewodzki Szpital Specjalietyczny	Biala Podlaska
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Centrum Onkologii Ziemi Lubelskiej im.	Lublin
Poland	Oddzial Onkologii Klinicznej, Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu	Poznan
United Kingdom	Edinburgh Cancer Centre, Western General Hospital	Edinburgh
United Kingdom	Medway NHS Foundation Trust	Gillingham	Kent
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	St James Hospital	Leeds
United Kingdom	Nottingham University Hospitals	Nottingham
United Kingdom	Cancer Institute Singleton Hospital	Swansea	Wales
United Kingdom	Somerset NHS Foundation Trust	Taunton	Somerset

Sponsors (1)

Lead Sponsor	Collaborator
Allarity Therapeutics

Countries where clinical trial is conducted

Belgium,  Finland,  Germany,  Italy,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Benefit Rate (CBR)	To evaluate the clinical benefit rate of ixabepilone using tumor measurements (e.g. CT or MRI etc.). One-sided comparisons of CBR between treatment and historic control will be performed, and will be repeated for subgroups defined by ER status.	1 year
Secondary	Progression free survival (PFS)	PFS defined as time from inclusion until progressive disease(PD) according to RECIST v 1.0 or death of any reason	1 year
Secondary	Overall survival (OS)	OS defined as time from inclusion until death	1 year
Secondary	Overall response rate (ORR) defined as CR + PR	Objective response rate (ORR) as defined as complete response (CR) + partial response (PR) according to RECIST v 1.0	1 year
Secondary	Incidence of Treatment-Emergent Adverse Events measured by NCI-CTCAE v.5.0	A description of the extent, duration and reversibility of ixabepilone elicited toxicity in target organs based on the Common Terminology Criteria for Adverse Events (NCI-CTCAE v.5.0)	1 year
Secondary	Clinical Benefit Rate (CBR) - fresh biopsy versus archival	Assess difference in prediction based on archival and fresh biopsy from same patient (percent agreement in binary prediction, and difference in primary and secondary endpoints with archival versus fresh biopsies)	1 year