Metastatic Breast Cancer
Conditions
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.
Interventions
DRUGIxabepilone Injection
Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle
Sponsors
Allarity Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) | Baseline to 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 1 year | PFS defined as time from inclusion until progressive disease(PD) according to RECIST v 1.0 or death of any reason |
| Overall Survival (OS) | 1 year | OS defined as time from inclusion until death |
| Overall Response Rate (ORR) Defined as CR + PR | 1 year | Objective response rate (ORR) as defined as complete response (CR) + partial response (PR) according to RECIST v 1.0 |
| Incidence of Treatment-Emergent Adverse Events Measured by NCI-CTCAE v.5.0 | 1 year | 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) |
| Clinical Benefit Rate (CBR) - Fresh Biopsy Versus Archival | 1 year | 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) |
Countries
Belgium, Finland, Germany, Italy, Netherlands, Poland, United Kingdom
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment Belgium | 6 participants |
| Region of Enrollment Netherlands | 1 participants |
| Region of Enrollment Poland | 3 participants |
| Region of Enrollment United Kingdom | 3 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 4 / 13 |
Outcome results
None listed