Locally recurrent or metastatic breast cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Ixabepilone
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: azaepothilone B
CAS Number: 219989-84-1
Other descriptive name: IXABEPILONE
Concen
Sponsors
Allarity Therapeutics Europe Aps
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form 2. Age 18 years or older 3. Patients with histologically or cytological confirmed adenocarcinoma of the breast and with confirmed locally recurrent or metastatic disease 4. Patients with hormone receptor positive and HER2 negative or triple negative primary tumor. 5. Previous chemotherapies (neoadjuvant, adjuvant or in the metastatic setting) must have included a taxane and an anthracycline unless anthracycline therapy is not indicated or not in use. 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 by RECIST v 1.1 criteria 8. Performance status of ECOG = 1 9. DRP-Ixempra-Breast score of >33% in archival biopsy or in a more recent biopsy. If two biopsies are available and disagree, the archival biopsy takes precedence. 10. Adequate conditions as evidenced by the following clinical laboratory values: a. Absolute neutrophils count (ANC) = 1.5 x 109/L b. Hemoglobin > 10 g/dL (6.2 mmol/L) c. Platelets = 100 x 109 /L d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN e. Serum bilirubin = 1.0 ULN f. Creatinine = 1.5 ULN g. Alkaline phosphatase = 2.5 x ULN or =5x ULN if documented liver/bone metastases. h. Blood urea within normal limits 11. Because of possible interference of cytochrome P450 3A4 activity by ixabepilone, patients will be 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. Negative pregnancy test at baseline 13. Women of childbearing age and potential must be willing to use highly effective contraception during the study and at least until 7 months 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 4 months 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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 malignancies 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: a. Stroke within = 6 months prior to day 1 b. Transient ischemic attach (TIA) within = 6 months prior to day 1 c. Myocardial infarction within = 6 months prior to day 1 d. Unstable angina e. New York Hart Association (NYHA) Class II or greater congestive heart failure (CHF) f. Serious cardiac arrhythmia requiring medication 8. 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 9. Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy 10. Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry) 11. Known prior severe hypersensitivity reactions to agents containing polyoxyethylated castor oil (Cremophor EL) 12. Patients must not continue treatment with strong inhibitors of CYP3A4 e.g.: ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole. These therapies should be discontinued 72 hours prior to initiation of study drug therapy. Similarly, patients must not continue treatment with strong inducers of CYP3A4 e.g.: phenytoin, carbamazepine, rifampin, rifabutin, dexamethasone, and phenobarbital. (20 mg dexamethasone can be used for pre-treatment if required). These therapies should be discontinued 72 hours prior to initiation of study drug therapy 13. Positive HIV and hepatitis B and C status, assessed from medical records only
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical benefit rate (CBR) of ixabepilone;Secondary Objective: •To evaluated progression free survival (PFS) •To evaluate overall survival (OS) •To evaluate objective response rate (ORR) defined as Complete Response (CR) and Partial Response (PR) •To evaluate the safety profile of ixabepilone in patient with locally recurrent or metastatic breast cancer •To further establish the clinical validation of the use of the DRP-Ixabepilone-Breast in selecting patients with locally recurrent or metastatic breast cancer •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);Primary end point(s): •Clinical Benefit Rate (CBR) will be defined as the proportion of patients having a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for at least 24 weeks;Timepoint(s) of evaluation of this end point: First tumor assessment is done at 6 weeks after start of IMP, then every 9 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS defined as time from the first IMP administration until progressive disease(PD) according to RECIST v 1.1 or death, whichever occurs first • OS defined as the time from the first IMP administration until death from any cause • ORR defined as the proportion of patients with complete response (CR) + partial response (PR) according to RECIST v 1.1 • Duration of response (DOR) defined as time of first documented CR or PR response until documented tumor progression (RECIST v 1.1);Timepoint(s) of evaluation of this end point: First tumour assessment is done at 6 weeks after start of IMP, then every 9 weeks. Patients who have received at least 2 cycles of treatment will be included in the per. protocol analyses. | — |
Countries
Finland, Netherlands, Poland
Contacts
Public ContactCharlotte Kleiveland
Smerud Medical Research International AS
Outcome results
None listed