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

Launched by FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI, MILANO · Dec 6, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for men with metastatic hormone-sensitive prostate cancer (mHSPC), which is a form of prostate cancer that has spread but is still responsive to hormone treatment. The trial will enroll about 566 participants and compare two groups: one group will receive a medication called apalutamide along with a local treatment (either radiotherapy or surgery) after six months, while the other group will continue with just the medication. This approach aims to see if adding local treatment can improve outcomes for patients.

To be eligible for this trial, participants must be men over 18 years old with confirmed prostate cancer that has spread to at least one bone. They should not have received previous hormone therapies or other treatments for prostate cancer, and must meet certain health criteria regarding their blood tests and overall physical condition. Participants can expect to receive regular care and monitoring throughout the study, and all will need to provide informed consent to participate. This trial is currently recruiting, and it's an opportunity for eligible patients to explore new treatment options.

Gender

MALE

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