Clinical Trials Register

Summary
EudraCT Number:	2014-005079-10
Sponsor's Protocol Code Number:	TOK-200-15
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-04-03
Trial results	View 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

Belgium - FPS Health-DGM

A.2

EudraCT number

2014-005079-10

A.3

Full title of the trial

ARMOR3-SV: A Phase 3, Randomized, Open-Label, Multi-Center, Controlled Study of Galeterone Compared with Enzalutamide in Men Expressing Androgen Receptor Splice Variant-7 mRNA with Metastatic Castration Resistant Prostate Cancer

A.3.1

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

A clinical trial comparing the effectiveness of galeterone compared to enzalutamide in men expressing Androgen Receptor Splice Variant-7 mRNA (AR-V7) with metastatic Castrate Resistant Prostate Cancer

A.3.2

Name or abbreviated title of the trial where available

ARMOR3-SV

A.4.1

Sponsor's protocol code number

TOK-200-15

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02438007

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	Tokai Pharmaceuticals Inc
B.1.3.4	Country	United States
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	Tokai Pharmaceuticals Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novella Clinical
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Novella Clinical
B.5.3.2	Town/ city	Stevenage
B.5.3.3	Post code	SG12ST
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441438221122
B.5.5	Fax number	00448707626257
B.5.6	E-mail	hcairns-gilliland@novellaclinical.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	Galeterone
D.3.2	Product code	TOK-001
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GALETERONE
D.3.9.1	CAS number	851983-85-2
D.3.9.3	Other descriptive name	GALETERONE
D.3.9.4	EV Substance Code	AS1
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	425
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	Comparator
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	Xtandi
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Xtandi
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Enzalutamide
D.3.9.1	CAS number	915087-33-1
D.3.9.4	EV Substance Code	AS2
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	40
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

Androgen receptor (AR) splice variant-7 (ARV7), metastatic (M1) castration resistant prostate cancer (CRPC)

E.1.1.1

Medical condition in easily understood language

A specific type of prostate cancer which does not respond when the hormone testosterone is blocked

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	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10007453
E.1.2	Term	Carcinoma of the prostate metastatic
E.1.2	System Organ Class	100000004864

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 of this study is to compare blinded, independent, centrally assessed radiographic progression-free survival (rPFS) in patients treated with daily oral galeterone (Experimental Arm) to patients treated with daily oral enzalutamide (Control Arm).

E.2.2

Secondary objectives of the trial

The key secondary objectives of this study include the following comparisons between galeterone-treated patients versus enzalutamide-treated patients:
1. Time to initiation of next active anti-cancer therapy for prostate cancer (eg AR signaling agents, investigational agents, cytotoxic chemotherapy)
2. Overall survival

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A patient who meets all of the following inclusion criteria will be eligible to participate in this study:
1) Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits, and provide authorization for Sponsor use and release of health and research trial information;
2) Male age > 18 years;
3) Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate (excluding pure/predominant neuroendocrine, sarcomatoid or squamous differentiation, or small cell histology);
4) Detectable AR-V7 mRNA transcript in CTCs as assessed by qRT-PCR performed at the central laboratory;
5) Castrate serum testosterone level: ≤ 50 ng/dL (1.73 nmol/L);
6) Bilateral orchiectomy (i.e., surgical castration) or ongoing androgen deprivation therapy (ADT) with a GnRH analogue or antagonist. Patients who have not had bilateral orchiectomy must maintain effective GnRH-analogue therapy for the duration of the trial;
7)Progressive disease confirmed by the treating physician at study entry (baseline) despite castrate serum testosterone, as defined as 1 or more of the following 3 criteria:
a. PSA progression defined by a minimum of 2 rising PSA levels measured at least 1 week apart. Patients who received anti-androgen treatment must have PSA progression after withdrawal (≥ 2 weeks since last flutamide, bicalutamide or nilutamide). PSA at Screening should be ≥ 2 μg/L (2 ng/mL);
b. Bone disease progression based on PCWG2 criteria defined by the presence of 2 or more new lesions on bone scan;
c. Soft tissue or visceral disease progression based on RECIST 1.1;;
8) Metastatic disease documented by bone lesions on bone scan or by soft tissue disease documented by CT/MRI as determined by the baseline central radiologic review. Per the American Joint Committee on Cancer (7th edition), M1 disease includes visceral/bony disease outside the true pelvis or pathologic (short axis lesion diameter ≥1.5cm) nodal involvement above the aortic bifurcation. Patients with evaluable disease limited to regional pelvic lymph nodes that reside anywhere within the pelvic inlet to the inguinal canals are not eligible;
9) Asymptomatic or mildly symptomatic pain due to prostate cancer (ie, the score on the BPI-SF Question #3 must be < 4) with or without the use of concomitant pain medication
10) Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
11) If sexually active with a woman of child-bearing age, must be willing to use 2 forms of adequate contraceptive methods (i.e., barrier contraception with spermicide) and continue use for 90 days after discontinuing study drug treatment (galeterone or enzalutamide);
12) Able to swallow up to six pills and retain oral medication;
13) Expected life expectancy of ≥ 6 months;
14) Able to adhere to study visit schedule and all protocol requirements.

E.4

Principal exclusion criteria

1)Participation in another clinical trial involving experimental therapy for CRPC within 4 weeks prior to first dose of study drug or simultaneous participation in a study involving investigational treatment;
2)Prior anti-cancer therapy:
a.Prior treatment with galeterone or any other investigational agent for metastatic prostate cancer
b.Prior treatment with second generation anti-androgens
c.Treatment with first generation anti-androgens within 2 weeks prior to first dose of study drug;
d.Prior treatment with CYP17 inhibitors
e.Ketoconazole use ≤2 weeks prior to first dose of study drug;
f.Prior radiation therapy (single fraction or radionuclide therapy [β or γ emitters]) within 2 weeks of first dose of study drug;
g. Prior treatment of bone metastases with radium Ra-223 dichloride (Xofigo®) (α emitters) ≤ 4 weeks prior to first dose of study drug. Treatment or plans to initiate treatment during the trial are prohibited;
h. Prior treatment with cytotoxic chemotherapy for CRPC, except patients may have received docetaxel for metastatic hormone sensitive prostate cancer; those patients must demonstrate continued disease progression and must not have received chemotherapy for at least 4 weeks prior to first dose of study drug;
i. Prior treatment with sipuleucel-T or other investigational cancer immunotherapy is allowed provided that the treatment has been completed ≥ 4 weeks prior to first dose of study drug, but treatment or plans to initiate treatment during the trial is prohibited.
3)Concurrent use of other anti-cancer agents except for the following:
a.Ongoing treatment with luteinizing hormone-release hormone agonists/antagonists
b.Bone loss prevention therapy with bone-sparing agents ; patients must be on a stable dose for at least 4 weeks prior to first dose of study drug;
4)Treatment with 5-alpha reductase inhibitors or estrogens ≤ 4 weeks prior to first dose of study drug;
5) Major surgery within 4 weeks prior to first dose of study drug;
6) Any use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 2 weeks of first dose of study drug;
7)The following laboratory findings:
a)Testosterone >50ng/dL
b)PSA <2 μg/L (2ng/mL)
c)Serum creatinine >2 times ULN
d)Bilirubin ≥ 1.5 times institutional ULN
e)Aspartate aminotransferase and/or alanine aminotransferase >2.5 times the ULN
f)Hemoglobin <9.0g/dL
g) Absolute neutrophil count <1.5x109/L
h) Platelets < 75 x 109/L;
i) Serum potassium (K+) <3.0mmol/L
j) Albumin <30 g/L
8) The following medical conditions:
a)New York Heart Association Class III or IV congestive heart failure
b)Myocardial infarction/unstable angina (within the 6 months prior to first dose of study drug);
c)History of clinically significant ventricular arrhythmia
d)History of long QT syndrome, Mobitz II 2nd or 3rd degree heart block without a permanent pacemaker in place
e)Bradycardia as defined by heart rate of <50 beats/min at Screening ECG
f)History of chronic or active Hepatitis B or Hepatitis C or other known chronic liver disease. Patients recovered from hepatitis are not excluded from the study.
g)Known HIV infection
h)Uncontrolled hypertension (defined as systolic blood pressure > 170 mmHg or diastolic blood pressure of > 105 mmHg measured on at least two occasions, two weeks apart) despite acceptable anti-hypertension therapy
i)Hypotension (defined as systolic blood pressure <90 mmHg)
j)History of adrenal insufficiency or hyperaldosteronism
k)Gastrointestinal disorders or gastric bypass surgery including lap bands that could interfere with the absorption of galeterone or enzalutamide
l)Serious active infections requiring systemic treatment or nonmalignant medical illnesses that are uncontrolled
m)History of seizure, concomitant use of any medication that may predispose to seizure, or any condition such as underlying brain injury with loss of consciousness, transient ischemic attack with the past 12 months, cerebral vascular accident, or brain arteriovenous malformation;
n)History of other malignancy in the past 5 years, other than curatively treated non-melanomatous skin cancer and superficial transitional cell carcinoma of the bladder;
o)History of (in the past 5 years) other malignancy, other than curatively treated non-melanomatous skin cancer and superficial transitional cell carcinoma of the bladder
p)Presence of confirmed brain metastases or cranial/spinal epidural disease
q)Known allergy to any of the treatment components
9)Any physical or mental condition or social situation that, in the opinion of the Investigator, may interfere with the patient’s ability to comply with the trial procedures, confound the ability to interpret data from the study or places the patient at unacceptable risk if he participates in this study
10)Current alcohol abuse or illicit drug use

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint in the study is radiographic progression-free survival (rPFS) defined as time from randomization to the occurrence of one of the following: radiographic evidence of disease progression using Prostate Cancer Working Group 2 (PCWG2) criteria for bone disease; and/or Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for soft tissue and/or visceral disease assessed by a blinded, independent central radiologic review; or death from any cause (whichever occurs first).

E.5.1.1

Timepoint(s) of evaluation of this end point

The projected time to realize the last required rPFS event is approximately 21.2-23 months from the start of enrollment.

E.5.2

Secondary end point(s)

The key secondary efficacy endpoints in the study are:
• Time to initiation of cytotoxic chemotherapy for prostate cancer
• Overall survival (OS) measured by time from randomization to time of death from any cause

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints are time to event 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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

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)

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

United States

E.8.7

Trial has a data monitoring committee

Yes

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 - long term follow-up will then be performed to collect data for secondary endpoints

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