Multimodal Approach in Patients With mHSPC. Randomized Trial of APA+ADT vs APA-ADT and Local Treatment

NCT05649943 | Recruiting

• 1 other identifier: APP
• Study Type: interventional
• Target: 566
• Locations: 1 country
• Sites: 3

Brief Summary

Italian multicenter study, will enroll \~566 pts with oligometastatic hormone sensitive prostate cancer who are candidates to receive treatment with apalutamide. After 6 months from the start of treatment, patients will be randomized to receive local treatment based on the investigator's choice ( either one between primary radiotherapy or cytoreductive prostatectomy), in addition to apalutamide, or to continue just with medical therapy.

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-Free Survival (rPFS)

  Evaluation of the efficacy of treatment with APA+ADT for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy compared to treatment with APA+ ADT alone in terms of Radiographic Progression-Free Survival (rPFS) in patients with hormone prostate adenocarcinoma -susceptible with low-volume metastatic disease.

  Up to 48 months

Secondary Outcomes (2)

• Local event - free survival

  Up to 48 months

• Local treatment - free survival

  Up to 48 months

Study Arms (2)

APA + ADT + RP/RT

OTHER

Apalutamide 240 mg, four 60 mg tablets as an oral single daily dose, according to clinical practice, plus Androgen Deprivation Therapy (ADT) plus clinician-driven choice local treatment with Radiotherapy or Radical Prostatectomy, six months after starting treatment with apalutamide

Drug: APA + ADT; Procedure: Local Treatmetn RT or RP

APA + ADT

OTHER

Apalutamide 240 mg, four 60 mg tablets as an oral single daily dose, according to clinical practice, plus Androgen Deprivation Therapy (ADT)

Drug: APA + ADT

Interventions

APA + ADT DRUG

All participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily. Apalutamide is distributed in Italy under the trade name of Erleada® 60 mg. All patients not undergoing surgical castration should also continue medical castration by taking a gonadotropin-releasing hormone (GnRHa) analogue during treatment.

Also known as: Apalutamide 240 mg + Androgen Deprivation Therapy

APA + ADT; APA + ADT + RP/RT

Local Treatmetn RT or RP PROCEDURE

Patients who will undergo radiotherapy as a local treatment must be treated according to the following scheme: External beam radiotherapy administered at 36 Gy in six consecutive weekly fractions of 6 Gy, or 55 Gy in 20 daily fractions of 2・75 Gy over 4 weeks. Radiation therapy will be given with the patient supine and with a full bladder and an empty rectum. The planned target volume is prostate only, with an 8 mm margin posteriorly and a 10 mm margin elsewhere. No RT on lymph nodes is foreseen. RT should begin 6 months after the first dose of apalutamide (+/- 2 weeks). Radical prostatectomy should be performed 6 months after the first dose of apalutamide (+/- 2 weeks).

Also known as: Local treatment with radiotherapy or radical prostatectomy, clinician-driven choice

APA + ADT + RP/RT

Eligibility Criteria

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

You may qualify if:

• Age \> 18
• Histologically confirmed diagnosis of prostate adenocarcinoma
• Metastatic disease documented by ≥1 bone lesion with Technetium 99m (99mTc) bone scan. Individuals with only one bone lesion should have confirmation of that lesion on CT or MRI.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) Grade ≤ 2
• No previous treatment with antiandrogens or GnRH analogues, or a treatment ≤ 3 months.
• No previous systemic or local treatment for prostate adenocarcinoma, including pelvic radiotherapy.
• Laboratory values at the time of screening:
• a. Neutrophils ≥ 1500/μL b. Hemoglobin ≥ 9.0 mg/μL (no transfusions in the past 28 days) c. Platelets ≥ 100,000/μL d. Creatinine ≤ 2 x upper limit of normal and serum albumin ≥ 3.0 g/dL f. Total bilirubin ≤ 1.5 x upper limit of normal \[NOTE: In subjects with Gilbert syndrome, if total bilirubin is \>1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤ 1.5 x ULN subjects may be eligible\]; g. AST and ALT ≤ 2.5 x upper limit of normal
• Able to swallow Apalutamide tablets whole.
• All subjects must sign an Informed Consent Form indicating that they understand the purpose of the study and its procedures and intend to participate. The subject must be willing and must be able to comply with the restrictions specified in this protocol.
• Age \>18 years
• Clinical stage cT3
• Robot-assisted radical prostatectomy with iliac obturator lymphadenectomy
• Surgical piece management criteria similar to Proteus criteria.

You may not qualify if:

• Pathologic findings consistent with small cell, ductal, or neuroendocrine prostate cancer.
• Known brain metastases.
• Lymph node metastases only.
• Visceral metastases.
• Patients not eligible for surgery or radiotherapy.
• Unacceptable increase in cardiovascular risk, defined as the occurrence of at least one of the following episodes in the 6 months prior to randomization: unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant thromboembolic events (e.g., pulmonary embolism), or clinically significant ventricular arrhythmias .
• Uncontrolled high blood pressure (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
• Previous treatment with antiandrogens, GnRH analogues, or other systemic treatments for adenocarcinoma of the prostate.
• Previous local treatment with surgery and/or radiotherapy.
• Any prior malignancy (except adequately treated basal cell carcinoma or a squamous cell skin carcinoma, superficial bladder carcinoma, or any other in situ carcinoma currently in complete remission) within 5 years of randomization.
• Known allergies, hypersensitivity or intolerance to the excipients of Apalutamide.
• Patients who, within 28 days prior to randomisation, have received:
• transfusions (red blood cells and/or platelets);
• hematopoietic growth factors;
• major surgery.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• ASST Santi Paolo e Carlo: collaborator
• European Institute of Oncology: collaborator

Study Sites (3)

European Institute of Oncology

Milan, Lombardy, 20141, Italy

NOT YET RECRUITING

ASST Santi Paolo e Carlo

Milan, Lombardy, 20153, Italy

NOT YET RECRUITING

Istituto Tumori Milano

Milan, Mi, 20156, Italy

RECRUITING

Related Publications (14)

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MeSH Terms

Interventions

Glutamyl Aminopeptidase; Androgen Antagonists; apalutamide; Radiotherapy

Intervention Hierarchy (Ancestors)

Aminopeptidases; Exopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloexopeptidases; Metalloproteases; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics

Study Officials

• Valentina Guadalupi, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valentina Guadalupi, MD

CONTACT

00390223903811; valentina.guadalupi@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 14, 2022
• Study Start: March 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: September 3, 2025

Record last verified: 2025-09

Locations

IT (3)