Clinical Trials Register

Summary
EudraCT Number:	2020-004610-35
Sponsor's Protocol Code Number:	AL-2001
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-08-16
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-004610-35

A.3

Full title of the trial

Phase II, open label, single arm study to investigate anti-tumor effect of ixabepilone in patients with locally recurrent metastatic breast cancer (mBC) selected by the ixabepilone Drug Response Prediction (DRP) after failure of an anthracycline and a taxane

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

AL-2001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Allarity Therapeutics
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Allarity Therapeutics
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Smerud Medical Research International AS
B.5.2	Functional name of contact point	Charlotte Kleiveland
B.5.3	Address:
B.5.3.1	Street Address	Postbox 81, Skøyen
B.5.3.2	Town/ city	Oslo
B.5.3.3	Post code	0212
B.5.3.4	Country	Norway
B.5.4	Telephone number	+4723272000
B.5.5	Fax number	+4723272001
B.5.6	E-mail	charlotte.kleiveland@smerud.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ixabepilone
D.3.4	Pharmaceutical form	Concentrate and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	azaepothilone B
D.3.9.1	CAS number	219989-84-1
D.3.9.3	Other descriptive name	IXABEPILONE
D.3.9.4	EV Substance Code	SUB33513
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Locally recurrent or metastatic breast cancer

E.1.1.1

Medical condition in easily understood language

Locally recurrent or metastatic breast cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the clinical benefit rate (CBR) of ixabepilone

E.2.2

Secondary objectives of the trial

• 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

E.2.3

Trial contains a sub-study

E.3

Principal 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.
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. Ixabepilone DRP - score of >67%
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 effective contraception during the study and at least until 30 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.

E.4

Principal 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. Known hypersensitivity to fluoropyrimidines;
13. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency;
14. 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
15. Positive HIV and hepatitis B and C status, assessed from medical records only

E.5 End points

E.5.1

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

E.5.1.1

Timepoint(s) of evaluation of this end point

First tumor assessment is done at 6 weeks after start of IMP, then every 9 weeks.

E.5.2

Secondary end point(s)

• PFS defined as time from randomisation until progressive disease(PD) according to RECIST v 1.1 or death, whichever occurs first
• OS defined as the time from randomization 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)

E.5.2.1

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.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of last patient

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-04

P. End of Trial
P.	End of Trial Status	Ongoing

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