Radiotherapy Combined With a LHRH (Ant)Agonist Versus Apalutamide in Patients With Biochemical Recurrence After RP

NCT03899077 | Recruiting Phase 2

• 1 other identifier: CTOR18001GZA
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 9

Brief Summary

This is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist (arm A) versus anti-androgen therapy (AAT) with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm) or 6 28-day cycles of apalutamide 240mg daily (interventional arm). The study will include a screening phase, treatment phase, and a post-treatment phase. The primary objective of the trial is to compare sexual function between the 2 groups based on the Expanded Prostate cancer Index Composite (EPIC)-26 sexual domain scores at 9 months after start of hormonal treatment.

Conditions

Cancer of Prostate

Outcome Measures

Primary Outcomes (1)

• EPIC-26 sexual domain score

  EPIC-26 sexual domain score (0 - 100 scale, with higher scores representing better sexual function)

  9 months after start of hormonal treatment

Secondary Outcomes (5)

• FACT-P quality of life global score

  9 months after start of hormonal treatment

• EORTC QLQ C30 quality of life score

  9 months after start of hormonal treatment

• EORTC QLQ PR25 quality of life score

  9 months after start of hormonal treatment

• Grade of acute toxicity

  After obtaining informed consent and up to 30 days after last dose

• PSA response rates

  0, 3, 6, and 9 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

The standard hormonal treatment in combination with salvage radiotherapy is ADT by a LHRH agonist or antagonist for 24 weeks. LHRH agonists and antagonists include leuprolide, goserelin, triptorelin, and degarelix.

Drug: Leuprorelin Acetate 45Mg Powder for Injection Suspension Vial; Drug: Goserelin Acetate 10.8 MG Subcutaneous Implant; Drug: Triptorelin Pamoate; Drug: Degarelix acetate

Arm B

EXPERIMENTAL

Patients will receive 6 cycles (each cycle is 30 days) of the study drug (4x 60mg tablets daily in a single intake).

Drug: Apalutamide

Interventions

Apalutamide DRUG

Apalutamide 240mg daily for 6 months (i.e. 6 28-day cycles); oral use

Arm B

Leuprorelin Acetate 45Mg Powder for Injection Suspension Vial DRUG

Leuprorelin acetate 45mg for 6 months; subcutaneous use

Arm A

Goserelin Acetate 10.8 MG Subcutaneous Implant DRUG

Goserelin acetate 10.8mg for 6 months; subcutaneous use

Arm A

Triptorelin Pamoate DRUG

Triptorelin pamoate 22.5mg for 6 months; intramuscular use

Arm A

Degarelix acetate DRUG

Degarelix acetate 80mg for 6 months; subcutaneous use

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, \> 18 years old.
• ECOG 0-1.
• Histologically confirmed adenocarcinoma of the prostate.
• Previous radical prostatectomy (RP), pT2-3, pN0 or pNx.
• PSA detectable with confirmed rise (at least 2 weeks apart) at least 8 weeks after RP.
• Hormone-naive disease.
• Patients amendable to take oral medication.
• Patients must have clinical laboratory values at screening:
• Hemoglobin 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
• Platelet count ≥100,000 x 109/µL independent of transfusion and/or growth factors within 3 months prior to randomization
• Serum albumin ≥3.0 g/dL
• Serum creatinine \<2.0 × upper limit of normal (ULN)
• Serum potassium ≥3.5 mmol/L
• Serum total bilirubin 1.5 × ULN (note: in subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<2.5 × ULN

You may not qualify if:

• Patients with severe erectile dysfunction according to international index of erectile function (IIEF-5) questionnaire (score 1-7).
• Allergies, hypersensitivity or known intolerance to the study drugs or excipients.
• History of any of the following:
• Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
• Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization.
• Current evidence of any of the following:
• Uncontrolled hypertension.
• Gastrointestinal disorder affecting absorption.
• Patients already included in another clinical trial involving an experimental drug.

Sponsors & Collaborators

• Cancer Research Antwerp: lead
• Janssen Pharmaceutica: collaborator

Study Sites (9)

OLVZ Aalst

Aalst, 9300, Belgium

RECRUITING

AZ Sint-Jan

Bruges, 8000, Belgium

RECRUITING

Hopital Erasme

Brussels, 1070, Belgium

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

CH Jolimont

Haine-Saint-Paul, 7100, Belgium

ACTIVE NOT RECRUITING

UZ Brussel

Jette, 1090, Belgium

ACTIVE NOT RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

CHU UCL Namur

Namur, 5000, Belgium

ACTIVE NOT RECRUITING

GZA

Wilrijk, Belgium

RECRUITING

Related Publications (1)

• Dirix P, Strijbos M, den Mooter TV, Liefhooghe N, Bruwaene SV, Uvin P, Ghysel C, Ost D, Schatteman P, Bral S, Engels B, den Begin RV, Otte FX, Roumeguere T, Palumbo S, Neybuch Y, Fonteyne V, Ost P, Dirix L. Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. Future Oncol. 2020 Jun;16(16):1083-1189. doi: 10.2217/fon-2020-0056. Epub 2020 May 1.

  PMID: 32356465 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Leuprolide; Powders; Goserelin; Injections, Subcutaneous; Triptorelin Pamoate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Dosage Forms; Pharmaceutical Preparations; Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Piet Dirix

  Gasthuis Zusters Antwerpen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ilse Van der Auwera

CONTACT

003234433759; ilse.vanderauwera@gza.be

Nele Smet

CONTACT

003234433759; nele.smet@gza.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 2, 2019
• Study Start: April 5, 2019
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (9)