Clinical Trials Register

Summary
EudraCT Number:	2021-006674-22
Sponsor's Protocol Code Number:	56021927PCR2046
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-10-13
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2021-006674-22

A.3

Full title of the trial

AD ASTRA (Androgen Deprivation with Apalutamide and STereotactic RAdiotherapy)
Prospective institutional phase II study of efficacy and safety of androgen deprivation with apalutamide in high-risk prostate cancer patients treated with extremely hypofractionated stereotactic radiotherapy.

AD ASTRA (Androgénna Deprivácia s Apalutamidom a STereotaktickou RÁdioterapiou)
Prospektívna inštitucionálna štúdia fázy II účinnosti a bezpečnosti androgénnej deprivácie s apalutamidom u pacientov s karcinómom prostaty s vysokým rizikom liečených ultra- hypofrakcionovanou stereotaktickou rádioterapiou.

A.3.1

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

AD ASTRA (Androgen Deprivation with Apalutamide and STereotactic RAdiotherapy)

AD ASTRA (Androgénna Deprivácia s Apalutamidom a STereotaktickou RÁdioterapiou)

A.3.2

Name or abbreviated title of the trial where available

AD ASTRA

A.4.1

Sponsor's protocol code number

56021927PCR2046

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	VÝCHODOSLOVENSKÝ ONKOLOGICKÝ ÚSTAV, a.s.
B.1.3.4	Country	Slovakia
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
B.4.2	Country	Slovakia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	TWMA, s.r.o.
B.5.2	Functional name of contact point	MUDr. Beata Čečetková, PhD.
B.5.3	Address:
B.5.3.1	Street Address	U Hájovny 901
B.5.3.2	Town/ city	Průhonice
B.5.3.3	Post code	252 43
B.5.3.4	Country	Czechia
B.5.4	Telephone number	+420724 004 731
B.5.6	E-mail	beata.cecetkova@twma.cz

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
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen - Cilag International N.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.3.4	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

Localized or a locally advanced high-risk prostate cancer

E.1.1.1

Medical condition in easily understood language

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10060862
E.1.2	Term	Prostate 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

The primary objective is the assessment of efficacy and safety of the combination of ADT, apalutamide and stereotactic radiotherapy on the localized or locally advanced high-risk prostate cancer. Efficacy assessment is determined by the biochemical control rate after 5 years, and biochemical progression is defined according to RTOG – ASTRO Phoenix consensus criteria (a rise by 2 ng/mL or more above the nadir PSA with the date of failure determined "at call"). Safety assessment is determined by the rate of clinically significant G2 and G3 gastrointestinal and genitourinary toxicity.

E.2.2

Secondary objectives of the trial

The secondary objectives are the assessment of patient´s quality of life using the validated questionnaires, and the assessment of metastasis free survival based on 68Ga PSMA PET/CT. Time to distant metastasis is defined as the time from enrollment to the date of the first occurrence of bone or soft tissue distant metastasis on 68Ga PSMA PET/CT.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject must be a man in the age of 18 – 79 years;
2. Each subject must sign an informed consent form (ICF) indicating that he understands the purpose and procedures required for the study and is willing to participate in the study. Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Indicated and planned to receive primary RT for prostate cancer;
4. Histologically confirmed adenocarcinoma of an intact prostate and one of the following risk factors for EUA high-risk localized or locally prostate cancer (see Attachment 1) at diagnosis:
• Localized high-risk prostate cancer: PSA >20 ng/ml or GS >7 (ISUP grade 4/5) or cT2c
• Locally advanced high-risk prostate cancer: cT3 – 4 or cN+, any PSA, any ISUP grade
Note: Documentation of clinical T stage (cT2c, cT3, cT4) may be obtained from any clinical assessment acceptable for clinical T staging including digital rectal examination (DRE) and MR. Documentation of N and M stage may be obtained from conventional imaging (technetium bone scan, and prostate MR or abdominopelvic CT) or molecular imaging (68Ga PSMA PET/CT).
5. Modified Charlson comorbidity index (CCI) ≤4 (Attachment 2);
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0 or 1 (Attachment 2);
7. Adequate organ function determined by the following local laboratory values:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x upper limit of normal (ULN); total bilirubin ≤1.5x ULN,
• Serum creatinine ≤2x ULN,
• Thrombocytes ≥140x10^9/l,
• Hemoglobin ≥120 g/l (no transfusion is allowed within 3 months prior to enrollment);
8. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 3 months following the last dose of study drug. Donation of sperm is not allowed during the Treatment Phase and for 3 months following the last dose of study drug.
9. Be able to swallow whole study drug tablets, undergo prostate MR, prostate seeds implantation and prostate radiotherapy in supine position.

E.4

Principal exclusion criteria

1. Presence of distant metastasis on conventional imaging or 68Ga PSMA/PET (clinical stage M1). Isolated pelvic nodal disease below the iliac vessels bifurcation (clinical stage N1) is not an exclusion.
2. Prior treatment with LHRH agonist/antagonist analogue or anti-androgen or both for >3 months prior to enrollment;
3. Bilateral orchiectomy;
4. History of pelvic radiation;
5. Prior systemic (e.g., chemotherapy) or local (e.g., radical prostatectomy, cryotherapy) treatment for prostate cancer;
6. Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer;
7. Prior treatment with systemic glucocorticoids ≤4 weeks prior to enrollment or subject expected to require long-term use of corticosteroids during the study;
8. Use of first-generation antiandrogen (e.g., bicalutamide) ≤4 weeks prior to enrollment;
9. Use of 5-α reductase inhibitors (e.g., dutasteride, finasteride) ≤4 weeks prior to enrollment;
10. Use of any investigational agent ≤4 weeks prior to enrollment;
11. Current chronic use of opioid analgesics, for ≥3 weeks for oral or ≥7 days for non-oral formulations;
12. Major surgery ≤4 weeks prior to enrollment;
13. History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to enrollment; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect);
14. Current or prior treatment with anti-epileptic medications for the treatment of seizures;
15. Gastrointestinal conditions affecting absorption;
16. Known or suspected contraindications or hypersensitivity to apalutamide or LHRH agonists/antagonist or any of the components of the formulations;
17. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject.

E.5 End points

E.5.1

Primary end point(s)

5 –year biochemical control rate defined as a percentage of surviving patients without biochemical progression after 5 years since the treatment start (assessed by Kaplan-Meier estimate)

E.5.1.1

Timepoint(s) of evaluation of this end point

7 years

E.5.2

Secondary end point(s)

Major secondary endpoint:
Metastasis free survival based on PSMA PET/CT (assessed by Kaplan-Meier estimate). Time to distant metastasis is defined as the time from enrollment to the date of the first occurrence of radiographic or pathological bone or soft tissue distant metastasis 68Ga PSMA PET/CT

Other secondary endpoints:
5 –year biochemical control rate with PSA <0.2 ng/mL
5 –year prostate cancer specific survival
5 – year overall survival (OS). OS is defined as the time from enrollment to date of death from any cause.
Incidence of acute and late side effects and complications associated with radiotherapy and systemic treatment evaluated by Common Terminology Criteria of Adverse Event (CTC AE) and Patient Reported Outcomes (PRO) including QoL questionnaires
Effect of the planned interventions on QoL (I-PSS, EPIC-26, FACT-P, EQ-5D-5L, PRO-CTCAE™ (short version))

E.5.2.1

Timepoint(s) of evaluation of this end point

7 years

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

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

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

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)

Post treatment follow-up 5 years

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

2022-12-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-22

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

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