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

Primary Purpose

Metastatic Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ixabepilone Injection
Sponsored by
Allarity Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 >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.

Sites / Locations

  • Antwerp University HospitalRecruiting
  • Onze-Lieve-VrouwziekenhuisRecruiting
  • Clin. Univ. Saint-LucRecruiting
  • CHU de Liege, Oncology DepartmentRecruiting
  • Tampere University HospitalRecruiting
  • Charité - Universitätsmedizin Berlin
  • Modena University Hospital
  • Ikazia Hospital RotterdamRecruiting
  • Wojewodzki Szpital SpecjalietycznyRecruiting
  • Uniwersyteckie Centrum KliniczneRecruiting
  • Centrum Onkologii Ziemi Lubelskiej im.Recruiting
  • Oddział Onkologii Klinicznej, Szpital Kliniczny Przemienienia Pańskiego UM w PoznaniuRecruiting
  • Medway NHS Foundation TrustRecruiting
  • Beatson West of Scotland Cancer CentreRecruiting
  • Somerset NHS Foundation TrustRecruiting
  • Cancer Institute Singleton HospitalRecruiting
  • Edinburgh Cancer Centre, Western General HospitalRecruiting
  • St James HospitalRecruiting
  • Nottingham University Hospitals

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ixabepilone

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
Overall survival (OS)
OS defined as time from inclusion until death
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
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)
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)

Full Information

First Posted
March 8, 2021
Last Updated
July 26, 2023
Sponsor
Allarity Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04796324
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
November 1, 2023 (Anticipated)
Study Completion Date
November 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allarity Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle.
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ixabepilone
Arm Type
Experimental
Arm Description
Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle
Intervention Type
Drug
Intervention Name(s)
Ixabepilone Injection
Intervention Description
Ixabepilone 40 mg/m2 is administered as a 3-h intravenous infusion Day 1 in a 3-week cycle
Primary Outcome Measure Information:
Title
Clinical Benefit Rate (CBR)
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
PFS defined as time from inclusion until progressive disease(PD) according to RECIST v 1.0 or death of any reason
Time Frame
1 year
Title
Overall survival (OS)
Description
OS defined as time from inclusion until death
Time Frame
1 year
Title
Overall response rate (ORR) defined as CR + PR
Description
Objective response rate (ORR) as defined as complete response (CR) + partial response (PR) according to RECIST v 1.0
Time Frame
1 year
Title
Incidence of Treatment-Emergent Adverse Events measured by NCI-CTCAE v.5.0
Description
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)
Time Frame
1 year
Title
Clinical Benefit Rate (CBR) - fresh biopsy versus archival
Description
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)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent form Age 18 years or older Patients with histologically or cytological confirmed carcinoma of the breast. Patients with locally recurrent or metastatic disease Patients with HR-positive, HER negative tumors or triple negative tumors Previous chemotherapies (neo, adjuvant or in the metastatic setting) must have included a taxane and an anthracycline unless anthracycline therapy is not indicated. Maximum of three (3) prior chemotherapies in the metastatic setting in addition to any number of prior lines of endocrine therapy Measurable disease Performance status of ECOG ≤ 1 With an Ixabepilone DRP - score of >33% Adequate conditions as evidenced by the following clinical laboratory values: Absolute neutrophils count (ANC) ≥ 1.5 x 109/L Hemoglobin > 6.2 mmol/L Platelets ≥ 100 x 109 /L Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN Serum bilirubin ≤ 1.0 ULN Alkaline phosphatase ≤ 2.5 x ULN or ≤5x ULN if documented liver/bone metastases. Creatinine ≤ 1.5 ULN Blood urea within normal limits 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 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: HER2 positive tumor Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period Patients with intracranial disease Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study Any active infection requiring parenteral or oral antibiotic treatment. Patients with grade 2, in case of diabetes grade 1 or greater neuropathy Clinically significant (i.e. active) cardiovascular disease: Stroke within ≤ 6 months prior to day 1 Transient ischemic attach (TIA) within ≤ 6 months prior to day 1 Myocardial infarction within ≤ 6 months prior to day 1 Unstable angina New York Hart Association (NYHA) Class II or greater congestive heart failure (CHF) Serious cardiac arrhythmia requiring medication 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. Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry) Known prior severe hypersensitivity reactions to agents containing polyoxyethylated castor oil (Cremophor EL) Known hypersensitivity to fluoropyrimidines; Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joëlle COLLIGNON, Dr.
Phone
3242844343
Email
veronique.loo@chuliege.be
First Name & Middle Initial & Last Name or Official Title & Degree
Veronique Loo
Phone
3242844343
Email
veronique.loo@chuliege.be
Facility Information:
Facility Name
Antwerp University Hospital
City
Antwerp
State/Province
Edegem
ZIP/Postal Code
2650
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Hélène Pieters
Phone
0032 (0)3 821 38 14
Email
marie-helene.pieters@uza.be
First Name & Middle Initial & Last Name & Degree
Jolien Op de Beeck
Phone
0032 (0)3 821 38 14
Email
jolien.opdebeeck@uza.be
First Name & Middle Initial & Last Name & Degree
Konstantinos Papadimitriou, Dr
Facility Name
Onze-Lieve-Vrouwziekenhuis
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Wachtelaer
Email
stephanie.wachtelaer@olvz-aalst.be
First Name & Middle Initial & Last Name & Degree
Greet Huygh
Facility Name
Clin. Univ. Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalie Blondeel
Phone
+32 2 764 42 14
Email
nathalie.blondeel@saintluc.uclouvain.be
First Name & Middle Initial & Last Name & Degree
Elodie Villar
Email
elodie.villar@saintluc.uclouvain.be
First Name & Middle Initial & Last Name & Degree
François Duhoux, Prof
Facility Name
CHU de Liege, Oncology Department
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maude Piron
Email
mpiron@chu.ulg.ac.be
First Name & Middle Initial & Last Name & Degree
Veronique Loo
Email
veronique.loo@chuliege.be
First Name & Middle Initial & Last Name & Degree
Joelle Collignon
Facility Name
Tampere University Hospital
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mia Lehtisaari
Phone
+358 3 3116 7640
Email
mia.lehtisaari@pshp.fi
First Name & Middle Initial & Last Name & Degree
Minna Tanner, MD
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monika Majer
Phone
+49 30 450 56 46 74
Email
monika.majer@charite.de
First Name & Middle Initial & Last Name & Degree
Stefanie Kreuzer
Phone
+49 30 450 56 46 74
Email
stefanie.kreuzer@charite.de
First Name & Middle Initial & Last Name & Degree
Verena Kiver, Dr
Facility Name
Modena University Hospital
City
Modena
ZIP/Postal Code
41124
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elissa Pettorelli
Phone
+39 059-4223134
Email
elisa.pettorelli@unimore.it
First Name & Middle Initial & Last Name & Degree
Federico Piacentini, MD
Facility Name
Ikazia Hospital Rotterdam
City
Rotterdam
ZIP/Postal Code
3083
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corry Leunis-de Ruiter
Phone
+31 102 975 217
Email
c.leunis@ikazia.nl
First Name & Middle Initial & Last Name & Degree
Jan Drooger, MD
Facility Name
Wojewodzki Szpital Specjalietyczny
City
Biala Podlaska
ZIP/Postal Code
21-500
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominika Karnecka
Email
dominika.karnecka@komed-ck.pl
First Name & Middle Initial & Last Name & Degree
Piotr Centkowski, MD
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdańsk
ZIP/Postal Code
80-214
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Gladysz
Phone
48585844560
Email
gladysz@gumed.com
First Name & Middle Initial & Last Name & Degree
Jacek Jassem, Prof
Facility Name
Centrum Onkologii Ziemi Lubelskiej im.
City
Lublin
ZIP/Postal Code
20-090
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Plottke
Phone
48664065546
Email
rplottke@cozl.eu
First Name & Middle Initial & Last Name & Degree
Aneta Dobrzyńska-Rutkowska
Facility Name
Oddział Onkologii Klinicznej, Szpital Kliniczny Przemienienia Pańskiego UM w Poznaniu
City
Poznań
ZIP/Postal Code
61-848
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elżbieta Puch, MSc, PhD
Email
eapuch.oncoclinicaltrials@gmail.com
First Name & Middle Initial & Last Name & Degree
Rodryg Ramlau, Prof
Facility Name
Medway NHS Foundation Trust
City
Gillingham
State/Province
Kent
ZIP/Postal Code
ME7 5NY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ekaterina Ivanova
Phone
44 (0) 1634976728
Email
e.ivanova@nhs.net
First Name & Middle Initial & Last Name & Degree
Maher Hadaki
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lesley Conway
Phone
44 (0) 1413017128
Email
Lesley.Conway@ggc.scot.nhs.uk
First Name & Middle Initial & Last Name & Degree
Iain MacPherson, MD
Facility Name
Somerset NHS Foundation Trust
City
Taunton
State/Province
Somerset
ZIP/Postal Code
TA1 5DA
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joanne Rogers
Email
Joanne.Rogers@SomersetFT.nhs.uk
First Name & Middle Initial & Last Name & Degree
Saiqa Spensley
Facility Name
Cancer Institute Singleton Hospital
City
Swansea
State/Province
Wales
ZIP/Postal Code
SA2 8QA
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emma Dangerfield
Phone
44 (0) 1792 285547
Email
Emma.Dangerfield@wales.nhs.uk.uk
First Name & Middle Initial & Last Name & Degree
Nia Viney
Phone
44 (0) 1792 285547
Email
Nia.Viney@wales.nhs.uk
First Name & Middle Initial & Last Name & Degree
Mark Davies
Facility Name
Edinburgh Cancer Centre, Western General Hospital
City
Edinburgh
ZIP/Postal Code
EH4 2XR
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Fethers
Phone
+44 131 537 1265
Email
nicholas.fethers@nhslothian.scot.nhs.uk
First Name & Middle Initial & Last Name & Degree
Rachel Neilson
Phone
+44 131 537 1265
Email
rachel.neilson@nhslothian.scot.nhs.uk
First Name & Middle Initial & Last Name & Degree
Olga Oikonomidou, MD
Facility Name
St James Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Barber
Phone
+44 113 206 0440
Email
amy.barber9@nhs.net
First Name & Middle Initial & Last Name & Degree
Chris Twelves, Prof
Facility Name
Nottingham University Hospitals
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Individual Site Status
Suspended

12. IPD Sharing Statement

Learn more about this trial

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

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