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

January 30, 2024 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary end point: To determine whether treatment with apalutamide in combination with androgen-deprivative therapy for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy has better efficacy than medical treatment with apalutamide + ADT alone in terms of radiographic progression-free survival (rPFS), specifically time to radiographic progression in soft tissue per RECIST 1.1 or in bone per PCWG3 criteria by investigator, or death. Secondary end points: To evaluate tumor shrinkage after locoregional approach and to evaluate short and long term side effects after locoregional surgery or RT, time to PSA progression, time to castration resistance, cancer specific survival, overall survival and quality of life according to EPIC-26 and EQ-5D-5L questionnaires.

Study Type

Interventional

Enrollment (Estimated)

566

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Lombardia
      • Milano, Lombardia, Italy, 20141
        • Not yet recruiting
        • European Institute of Oncology
        • Contact:
        • Principal Investigator:
          • Barbara Alicja Jereczek, MD
      • Milano, Lombardia, Italy, 20153
        • Not yet recruiting
        • ASST Santi Paolo e Carlo
        • Contact:
        • Principal Investigator:
          • Bernardo Rocco, MD
    • Mi
      • Milan, Mi, Italy, 20156
        • Recruiting
        • Istituto Tumori Milano
        • Contact:
          • MD
        • Contact:
        • Principal Investigator:
          • Valentina Guadalupi, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: APA + ADT + RP/RT
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

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.

Other Names:
  • Apalutamide 240 mg + Androgen Deprivation Therapy
Procedure: Local Treatmetn RT or RP

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).

Other Names:
  • Local treatment with radiotherapy or radical prostatectomy, clinician-driven choice
Other: APA + ADT
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

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.

Other Names:
  • Apalutamide 240 mg + Androgen Deprivation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic Progression-Free Survival (rPFS)
Time Frame: Up to 48 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local event - free survival
Time Frame: Up to 48 months
Defined as the absence of one of the following conditions in the follow up: urinary retention, hydronephrosis, acute or chronic renal failure exacerbation, intestinal obstruction
Up to 48 months
Local treatment - free survival
Time Frame: Up to 48 months
Defined as the absence of the need for one of the following interventions: trans-urethral resection of the prostate, placement of a ureteral stent or nephrostomy for hydronephrosis, bladder catheterization, surgery for intestinal obstruction/colostomy
Up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborators

European Institute of Oncology
ASST Santi Paolo e Carlo

Investigators

  • Principal Investigator: Valentina Guadalupi, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2023

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

December 6, 2022

First Submitted That Met QC Criteria

December 6, 2022

First Posted (Actual)

December 14, 2022

Study Record Updates

Last Update Posted (Actual)

January 31, 2024

Last Update Submitted That Met QC Criteria

January 30, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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