Clinical Trials Register

Summary
EudraCT Number:	2021-003523-16
Sponsor's Protocol Code Number:	ARN-I-20-DEU-003-V01
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-02
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

Germany - BfArM

A.2

EudraCT number

2021-003523-16

A.3

Full title of the trial

A feasibility trial investigating inductive Apalutamide therapy combined with radical prostatectomy in patients with locally advanced T4 high risk prostate cancer

A.3.1

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

n.a.

A.3.2

Name or abbreviated title of the trial where available

INDUCTA

A.4.1

Sponsor's protocol code number

ARN-I-20-DEU-003-V01

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	Universität des Saarlandes
B.1.3.4	Country	Germany
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	Janssen-Cilag GmbH, Neuss
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universität des Saarlandes
B.5.2	Functional name of contact point	Klinik für Urologie
B.5.3	Address:
B.5.3.1	Street Address	Campus
B.5.3.2	Town/ city	Saarbrücken
B.5.3.3	Post code	66123
B.5.3.4	Country	Germany
B.5.4	Telephone number	00490684116 24702
B.5.6	E-mail	michael.stoeckle@uks.eu

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	Erleada 60 mg Filmtabletten
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	Germany
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	Erleada 60 mg Filmtabletten
D.3.4	Pharmaceutical form	Film-coated 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	Apalutamide
D.3.9.1	CAS number	956104-40-8
D.3.9.4	EV Substance Code	SUB189031
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	60
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

patients with locally advanced T4 high risk prostate cancer

E.1.1.1

Medical condition in easily understood language

patients with locally advanced T4 high risk prostate cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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 assess operability in patients with locally advanced T4 high risk prostate cancer upon inductive pre-prostatectomy treatment with apalutamide plus ADT for a duration of up to 6 months.

E.2.2

Secondary objectives of the trial

Secondary objectives are
• to assess the feasibility of treatment
• to assess the effect of the treatment on patients’ quality of life
• to characterize PSA levels post-surgery without any further therapy and biochemical complete remission 6 months after surgery
• to describe the time to biochemical recurrence (BCR)
• to assess complete pathological response and negative margin status
• to assess safety and tolerability of treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male of 18 to 80 years of age, inclusive.
2.Histologically confirmed adenocarcinoma of the prostate without complete neuroendocrine differentiation or small cell features
3.cT4 PCa, considered as primary inoperable because of a fixed mass defined by digital rectal examination, confirmed by advanced disease in MRI
4.Eastern Cooperative Oncology Group Performance Status 0 or 1, patients must and are expected to be fit and willing to undergo radical prostatectomy within 6 to 9 months after start of study treatment
5.Adequate organ function determined by the following laboratory values:
a.Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin less than twice the upper limit of normal
b.Platelets ≥100,000/L, independent of transfusion and/or growth factors within 1 month prior to enrolment
6.At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors and estrogens prior to enrolment
7.No irradiation of the pelvis
8.Be able to swallow whole study drug tablets
9.Not candidate for radiotherapy or who deny radiotherapy
10.Must agree to wear a condom when engaging in any activity that allows for passage of ejaculate to another person while on study drug and for 3 months following the last dose of study drug
11.Must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last dose of IMP
12.Must sign an ICF indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study.

E.4

Principal exclusion criteria

1.Presence of distant metastasis (clinical stage M1) after MRI, CT abdomen and bone scan
Note: Patients with distant metastases only detectable in PSMA-PET/CTs are allowed to be included in the trial when conventional imaging (CT and bone scan) is negative for distant metastases
2.Pathological finding consistent with small cell, ductal, or complete neuroendocrine prostate cancer
3.Prior treatment with second generation anti-androgens
4.Prior treatment with CYP17 inhibitors
5.Prior treatment with systemic glucocorticoids ≤4 weeks prior to enrolment or patient expected to require long-term use of corticosteroids during the study
6.Use of 5-α reductase inhibitors (eg, dutasteride, finasteride) ≤4 weeks prior to enrolment
7.Major surgery ≤4 weeks prior to enrolment
8.Prior treatment with radiopharmaceutical agents
9.Prior chemotherapy for prostate cancer
10.History of any pelvic radiation
11.Bilateral orchiectomy
12.History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to enrolment; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months; uncontrolled hypertension; history of seizure or convulsion; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures
13.Presence of any of the following cardiologic criteria:
a) Mean resting QTc >470 msec
b) In patients with a history of risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval, the benefit-risk ratio including the potential for Torsade de pointes will be carefully assessed and patients will be excluded if the benefit-risk ratio is considered as unfavorable.
14.Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
15.Any active infection requiring systemic therapy
16.Known or suspected contraindications or hypersensitivity to apalutamide, or GnRH agonists or any of the components of the formulations
17.Patient is eligible for PROTEUS study (all patients with operable, non T4 disease)
18.Patient has received another investigational medication (including investigational vaccines) or used another invasive investigational medical device within 30 days before the planned first dose of the IMP of this study or is currently enrolled in another investigational study.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is the proportion of patients with operability - as assessed by MRI (experienced radiologist), transrectal ultrasound, and clinical examination (two experienced uro oncological surgeons) - upon inductive pre-prostatectomy treatment for a duration of up to 6 months. For patients who have not reached the PSA nadir after the 6-month period and are not considered as operable, the inductive therapy with apalutamide plus ADT can be expanded for a maximum of additional 3 months until the nadir is reached.

E.5.1.1

Timepoint(s) of evaluation of this end point

Upon inductive pre-prostatectomy treatment of 6 months. For patients who have not reached the PSA nadir after the 6-month period and are not considered as operable, the inductive therapy with apalutamide plus ADT can be expanded for a maximum of additional 3 months until the nadir is reached.

E.5.2

Secondary end point(s)

Secondary endpoints of this study are:
• Proportion of patients with pT0 (pCR) in prostatectomy specimens (complete pathological response)
• Proportion of patients with negative margin specimen from prostatectomy according to the histology results after surgery
• Proportion of patients with <pT2 in prostatectomy specimens
• Proportion of patients with post-prostatectomy complete biochemical remission (non-detectable serum PSA) 6 months after surgery without hormonal treatment
• Proportion of patients with post-prostatectomy complications requiring surgical re-intervention (Clavien-Dindo IIIB complications, except for interventions aiming at hemostasis only) during the entire post-prostatectomy period
• Proportion of patients who achieve PSA nadir upon 6 months of inductive treatment
• Proportion of patients who achieve PSA nadir, prior to surgery
• Change from baseline in FACT-P scores (FACT-P Trial Outcome Index, FACT-G total score, and FACT-P total score) at different study visits.
• Proportion of patients with improvement in their FACT-P scores compared to baseline at different study visits.
• Change from baseline in EQ-5D-3L score at different study visits.
• Proportion of patients with improvement in the EQ-5D-3L score compared to baseline at different study visits.
• Proportion of patients with early (ie, before prostatectomy) PSA relapse from nadir, defined as an absolute PSA increase of more than 10% from the initial PSA value prior to therapy with two PSA rises after 2 consecutive measurements within 2 weeks.
• Proportion of patients with biochemical recurrence (BCR), defined as 2 consecutive PSA values >0.2 ng/mL and rising obtained at two consecutive scheduled study visits after prostatectomy.
• Time to biochemical recurrence (BCR) after prostatectomy, if possible.
• The change in ECOG performance status as well as the change in some hematologic parameters (hemoglobin, leukocytes, lymphocytes, neutrophils, platelets), and the change in levels of serum testosterone/hormones from baseline at different study visits.
• Time to treatment discontinuation.
• Safety and tolerability with regard to adverse events (AEs), abnormal laboratory results, and perioperative complications.

E.5.2.1

Timepoint(s) of evaluation of this end point

Different timepoints depending on the end point. For details please refer to section E.5.2

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

Yes

E.6.4

Safety

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

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

The study is considered completed with the last visit for the last patient participating in the study.

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

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

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)

All patients who discontinue participation in the study will undergo a Study Discontinuation Visit (SDV), will also undergo usual standard of care regimens, and will be followed until end of the 6-month follow-up phase. If the Study Discontinuation Visit occurs ≥21 days after the last scheduled visit, procedures of the next scheduled visit should be done. Patients who discontinue treatment will be followed until the follow-up phase of 6 months ends.

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

2021-12-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-12-13

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

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