Inducta

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaet Des Saarlandes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Feb 2022 → 16 Sep 2025

Decision date (initial)

2024-01-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

University of Saarland · This study is financially supported by Janssen-Cilag GmbH, Neuss

External identifiers

EU CT number

2023-509837-37-00

EudraCT number

2021-003523-16

WHO UTN

U1111-1302-2568

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

The primary objective of this study is to assess operability in patients with locally advanced T4 high risk prostate cancer upon inductive preprostatectomy
treatment with apalutamide plus ADT for a duration of up to 6 months.

Secondary objectives 6

1. to assess the feasibility of treatment
2. to assess the effect of the treatment on patients' quality of life
3. to characterize PSA levels post-surgery without any further therapy and biochemical complete remission 6 months after surgery
4. to describe the time to biochemical recurrence (BCR)
5. to assess complete pathological response and negative margin status
6. to assess safety and tolerability of treatment

Conditions and MedDRA coding

Patients with locally advanced T4 high risk prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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.

Exclusion criteria 18

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The prim endpoint of this study is the proportion of pat. with operability - as assessed by MRI , 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 additiona

Secondary endpoints 17

1. Proportion of patients with pT0 (pCR) in prostatectomy specimens (complete pathological response)
2. Proportion of patients with negative margin specimen from prostatectomy according to the histology results after surgery
3. Proportion of patients with
4. Proportion of patients with post-prostatectomy complete biochemical remission (non-detectable serum PSA) 6 months after surgery without hormonal treatment
5. 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 postprostatectomy period
6. Proportion of patients who achieve PSA nadir upon 6 months of inductive treatment
7. Proportion of patients who achieve PSA nadir, prior to surgery
8. 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.
9. Proportion of patients with improvement in their FACT-P scores compared to baseline at different study visits.
10. Change from baseline in EQ-5D-3L score at different study visits.
11. Proportion of patients with improvement in the EQ-5D-3L score compared to baseline at different study visits.
12. 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.
13. 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.
14. Time to biochemical recurrence (BCR) after prostatectomy, if possible.
15. 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
16. Time to treatment discontinuation.
17. Safety and tolerability with regard to adverse events (AEs), abnormal laboratory results, and perioperative complications.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Des Saarlandes

Sponsor organisation

Universitaet Des Saarlandes

Address

Kirrberger Strasse 100

City

Homburg

Postcode

66421

Country

Germany

Scientific contact point

Organisation

Universitaet Des Saarlandes

Contact name

Prof. Stöckle

Public contact point

Organisation

Universitaet Des Saarlandes

Contact name

Prof. Stöckle

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications