Combination treatment for metastatic hormone-sensitive prostate cancer

APPROACH : Multimodal Approach in Patients With mHSPC. A Pragmatic Randomized Trial of Apalutamide Plus Androgen Deprivation Therapy (APA-ADT) Versus APA-ADT Plus Local Treatment. A Meet-URO 29 Study

This study is testing whether adding local treatment like radiation or surgery to a hormone therapy for prostate cancer helps patients live longer without their cancer getting worse.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 566 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Academic / other)
• Locations: 3 sites (Milan, Lombardy and 2 other locations)
• Trial ID: NCT05649943 on ClinicalTrials.gov

What this trial studies

This Italian multicenter study aims to enroll approximately 566 patients with oligometastatic hormone-sensitive prostate cancer who are eligible for treatment with apalutamide. After six months of treatment, participants will be randomized to receive either local treatment (radiotherapy or prostatectomy) alongside apalutamide and androgen deprivation therapy (ADT), or to continue with apalutamide and ADT alone. The primary endpoint is to assess the efficacy of the combined treatment in terms of radiographic progression-free survival, while secondary endpoints include evaluating tumor shrinkage, side effects, and overall survival. The study seeks to determine the best approach to improve patient outcomes in this specific cancer population.

Who should consider this trial

Good fit: Ideal candidates for this study are adult males over 18 years old with histologically confirmed metastatic hormone-sensitive prostate cancer and specific eligibility criteria.

Not a fit: Patients who have previously received antiandrogens or GnRH analogues, or those with extensive prior treatments for prostate cancer, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment strategy for patients with metastatic hormone-sensitive prostate cancer, potentially improving survival rates.

How similar studies have performed: Other studies have shown promising results with similar multimodal approaches in treating metastatic prostate cancer, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* 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.

Inclusion criteria for cytoreductive surgery:

* Age \>18 years
* Clinical stage cT3
* Robot-assisted radical prostatectomy with iliac obturator lymphadenectomy
* Surgical piece management criteria similar to Proteus criteria.

Exclusion Criteria:

* 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:

  1. transfusions (red blood cells and/or platelets);
  2. hematopoietic growth factors;
  3. major surgery.
* Symptomatic and/or chronic viral hepatitis; chronic liver disease; moderate or severe liver failure (class B and C according to the Child-Pugh scale); encephalopathy, ascites or thrombo-haemorrhagic disorders secondary to liver failure.
* Gastrointestinal disorders affecting drug absorption
* Active infections requiring systemic therapy such as human immunodeficiency virus (HIV);
* Any condition or situation which, in the judgment of the investigator, precludes participation in this trial.

Exclusion criteria for cytoreductive surgery:

* Contraindication for surgery

Where this trial is running

Milan, Lombardy and 2 other locations

• European Institute of Oncology — Milan, Lombardy, Italy (Not_yet_recruiting)
• ASST Santi Paolo e Carlo — Milan, Lombardy, Italy (Not_yet_recruiting)
• Istituto Tumori Milano — Milan, Mi, Italy (Recruiting)

Study contacts

• Principal investigator: Valentina Guadalupi, MD — Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Study coordinator: Valentina Guadalupi, MD

Conditions Metastatic Hormone-Sensitive Prostate Cancer