Clinical Trials Register

Summary
EudraCT Number:	2015-000270-36
Sponsor's Protocol Code Number:	AbiCab
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-03-11
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

Sweden - MPA

A.2

EudraCT number

2015-000270-36

A.3

Full title of the trial

A randomized Phase II, open label multicenter cross-over study, to evaluate biomarkers, in 2nd line treatment of metastatic Castration Resistant Prostate Cancer (mCRPC) with abiraterone and cabazitaxel

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

AbiCab

A.4.1

Sponsor's protocol code number

AbiCab

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	Umeå University Hospital
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	sanofi
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Stiftelsen för Strategisk Forskning,
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Umeå University Hospital
B.5.2	Functional name of contact point	Sponsor
B.5.3	Address:
B.5.3.1	Street Address	Department of oncology
B.5.3.2	Town/ city	Umeå
B.5.3.3	Post code	SE-90185
B.5.3.4	Country	Sweden
B.5.6	E-mail	camilla.thellenberg@onkologi.umu.se

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	Yes
D.2.1.1.1	Trade name	Zytiga
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	ZYTIGA 250 mg tabletter
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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.IMP: 2
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	Yes
D.2.1.1.1	Trade name	Jevtana
D.2.1.1.2	Name of the Marketing Authorisation holder	sanofi-aventis groupe
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	JEVTANA 60 mg koncentrat och vätska till infusionsvätska, lösning
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.3.11 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

Metastatic Castration Resistant Prostate Cancer

E.1.1.1

Medical condition in easily understood language

Metastatic Castration Resistant Prostate 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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
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

The primary objective is to evaluate if tumor expression levels of the biomarker AKR1C3 can predict mCRPC patient PSA response to therapy with abiraterone or cabazitaxel, during the first treatment period.

E.2.2

Secondary objectives of the trial

I. To evaluate if tumor expression levels of the biomarker AR-V7 can predict mCRPC patient PSA response to therapy with abiraterone or cabazitaxel, during the first treatment period.
II. Investigate if baseline tumor expression levels of AR-V7 and AKR1C3 can be used to select what sequence of treatment (abi+cab vs cab+abi) is most likely to result in successful treatment.
III. Investigate if treatment with abiraterone and or cabazitaxel result in different resistance mechanisms with respect to induction of AR splice variants or other resistance mechanisms.
IV. Validate tissue markers in bloodbased entities (“liquid biopsies”) such as Exosomes, Trombocytes and Circulating Tumor Cells (CTCs).
V. Comparison of PSA progression free survival, Radiologic progression free survival in relation to assigned first treatment according to biomarker status and overall survival in relation to both treatment periods according to biomarker status.
VI. Safety

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed Informed Consent
2. Histological confirmed prostate cancer
3. Macroscopic metastatic disease previous treated with docetaxel
4. Castration resistant disease defined as:
a) Plasma testosterone (< 0.5 ng/ml) and
b) Increase in measurable disease (Recist 1.1) Or
c) Appearance of new lesions on bone scintigrams Or
d) Rising PSA, two consecutive rising values at least one week apart.
5. Metastatic tumour containing biopsy (Crista iliaca or CT/Ultrasound-guided biopsy)

E.4

Principal exclusion criteria

1. Less than 4 weeks since prior treatment with chemotherapy,
2. Less than 4 weeks days since radiotherapy or surgery to the start, bone pain palliative radiotherapy is allowed
3. Less than 4 weeks after stopping endocrine therapies including anti-androgen.
4. No “new drugs” (ie abiraterone, enxalutamide, Ra223 and other) given in mCRPC stage will be allowed to ensure that the trial is strictly second line after Docetaxel.
5. Prior isotope therapy or radiotherapy to > 30% of bone marrow (whole pelvic radiotherapy is not an exclusion criteria)
6. Use of other investigational drug therapy for any reason is prohibited.
7. Persistent adverse events from previous cancer therapies > grade 1 (NCI CTCAE V4.03) with the exception of alopecia. (With respect to nail changes grade 2 is acceptable)
8. Symptomatic peripheral neuropathy grade >2 (NCI CTCAE] v.4.03.
9. Age less than 18 years
10. ECOG performance status > 2
11. Known CNS malignancy
12. Within 6 months of randomization: myocardial infarction , unstable angina, angioplasty, bypass surgery, stroke, TIA, or congestive heart failure NYHA class III or IV
13. Within 3 months prior to randomization: treatment resistant peptic ulcer disease, infectious or inflammatory bowel disease, pulmonary embolism
14. Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results
15. Unable to comply with study procedures
16. Patients with reproductive potential not implementing accepted and effective method of contraception.
17. History of severe hypersensitivity reaction (≥grade 3) to docetaxel
18. History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
19. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
20. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix A and B)
21. Inadequate organ and bone marrow function as evidenced by:
a) Hemoglobin <10.0 g/dL
b) Absolute neutrophil count <1.5 x 109/L,
c) Platelet count <100 x 109/L,
d) AST/SGOT and/or ALT/SGPT >1.5 x ULN;
e) Total bilirubin >1 x ULN,
22. Serum creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded

E.5 End points

E.5.1

Primary end point(s)

The proportion of patients with PSA response ≥ 50% after treatment with Abiraterone or Cabazitaxel in the first treatment period before cross over comparing groups defined by AKR1C3 levels as high or low at baseline

E.5.1.1

Timepoint(s) of evaluation of this end point

At progression after the first treatment period before cross over.

E.5.2

Secondary end point(s)

I. The proportion of patients with PSA response ≥ 50% after treatment with Abiraterone or Cabazitaxel in the first treatment period before crossover comparing groups defined by AR-V7 presence or abscence at baseline.
II. The summary of the combined PSA progression free survival in the two treatment periods comparing groups defined by the combined AKR1C3 and AR-V7 patterns at baseline and sequence of treatments.
III. The proportion of patients that have low expression of AR-V7 at baseline and who develops high expression during therapy with Abiraterone differs compared to corresponding group that receives Cabazitaxel as measured at first progression.
IV. Blood based expression of biomarkers correlates to tissue based expression of the same markers.
V. Progression free survival endpoints
a. PSA and radiological PFS,
b. Overall survival
VI. Safety

VII. Exploratory endpoints
• Search for new biomarkers
• Improvement in Pain Control
• Quality of Life /FACT_P)
• BSI (Bone Scan Index) in relation to PCGW2

E.5.2.1

Timepoint(s) of evaluation of this end point

I. At progression after the first treatment period before cross over.
II. End of study
III. At progression after the first treatment period before cross over
IV. End of study
V. End of study
VI. During the study
VII. During the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

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

Yes

E.8.1.1

Randomised

Yes

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

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

LVLS

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

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

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-05-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-27

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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