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Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)APPROACHNCT05649943

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

A study testing APA + ADT and Local Treatmetn RT or RP in people with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC), run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 3 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
APA + ADT and Local Treatmetn RT or RP
Could I receive a placebo?
No, everyone receives an active treatment
How many people
566 participants
Where
3 sitesItaly
Study dates
1 Mar 2023to 1 Jan 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Laboratory values at the time of screening:
  • 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.

Who cannot join

  • 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 .
Show all 20Show fewer
  • 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.
  • 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.
  • Contraindication for surgery

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Valentina Guadalupi, MD contact

00390223903811

valentina.guadalupi@istitutotumori.mi.it

Italy3 sites, 3 recruiting

  • European Institute of Oncology

    Milan, Lombardy, 20141

    Barbara Alicja Jereczek, MD, barbara.jereczek@ieo.it

    Barbara Alicja Jereczek, MD

    Not yet recruiting

  • ASST Santi Paolo e Carlo

    Milan, Lombardy, 20153

    Bernardo Rocco, MD, bernardo.rocco@gmail.com

    Bernardo Rocco, MD

    Not yet recruiting

  • Istituto Tumori Milano

    Milan, Mi, 20156

    Valentina Guadalupi, MD, +390223902811, valentina.guadalupi@istitutotumori.mi.it

    MD

    Recruiting

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
APA + ADT, Local Treatmetn RT or RP

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APA + ADTDrug

    Also called Apalutamide 240 mg + Androgen Deprivation Therapy

    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.

  • Local Treatmetn RT or RPProcedure or surgery

    Also called Local treatment with radiotherapy or radical prostatectomy, clinician-driven choice

    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).

Study groups in NCT05649943
Study groupRoleWhat they receive
APA + ADT + RP/RTOtherApalutamide 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
Receives: Drug: APA + ADT; Procedure: Local Treatmetn RT or RP
APA + ADTOtherApalutamide 240 mg, four 60 mg tablets as an oral single daily dose, according to clinical practice, plus Androgen Deprivation Therapy (ADT)
Receives: Drug: APA + ADT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 48 months

Secondary outcomes (2)

  1. Local event - free survival

    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

    Measured: Up to 48 months

  2. Local treatment - free survival

    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

    Measured: Up to 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2022
  2. Study start1 Mar 2023
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized
Masking
None (open label)
Enrolment
566 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05649943
Sponsor's protocol ID
APP
Acronym
APPROACH
Status last verified
Sep 2025
First submitted
6 Dec 2022
Last updated
3 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez Soto A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. doi: 10.1056/NEJMoa1903307. Epub 2019 May 31.

    PubMed 31150574

  • Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158. doi: 10.1016/j.eururo.2020.08.011. Epub 2020 Sep 6.

    PubMed 32907777

  • Metcalfe MJ, Smaldone MC, Lin DW, Aparicio AM, Chapin BF. Role of radical prostatectomy in metastatic prostate cancer: A review. Urol Oncol. 2017 Apr;35(4):125-134. doi: 10.1016/j.urolonc.2017.01.001. Epub 2017 Feb 9.

    PubMed 28190749

  • Mathieu R, Korn SM, Bensalah K, Kramer G, Shariat SF. Cytoreductive radical prostatectomy in metastatic prostate cancer: Does it really make sense? World J Urol. 2017 Apr;35(4):567-577. doi: 10.1007/s00345-016-1906-3. Epub 2016 Aug 8.

    PubMed 27502935

  • Gravis G, Boher JM, Joly F, Soulie M, Albiges L, Priou F, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Theodore C, Deplanque G, Ferrero JM, Culine S, Mourey L, Beuzeboc P, Habibian M, Oudard S, Fizazi K; GETUG. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. 2016 Aug;70(2):256-62. doi: 10.1016/j.eururo.2015.11.005. Epub 2015 Nov 21.

    PubMed 26610858

  • Inaba K, Tsuchida K, Kashihara T, Umezawa R, Takahashi K, Okuma K, Murakami N, Ito Y, Igaki H, Sumi M, Nakayama Y, Shinoda Y, Hara T, Matsui Y, Komiyama M, Fujimoto H, Itami J. Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer. J Radiat Res. 2021 May 12;62(3):511-516. doi: 10.1093/jrr/rraa056.

    PubMed 33822986

  • Heidenreich A, Pfister D, Porres D. Cytoreductive radical prostatectomy in patients with prostate cancer and low volume skeletal metastases: results of a feasibility and case-control study. J Urol. 2015 Mar;193(3):832-8. doi: 10.1016/j.juro.2014.09.089. Epub 2014 Sep 22.

    PubMed 25254935

  • Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol. 2014 Jun;65(6):1058-66. doi: 10.1016/j.eururo.2013.11.012. Epub 2013 Nov 20.

    PubMed 24290503

  • Sooriakumaran P, Karnes J, Stief C, Copsey B, Montorsi F, Hammerer P, Beyer B, Moschini M, Gratzke C, Steuber T, Suardi N, Briganti A, Manka L, Nyberg T, Dutton SJ, Wiklund P, Graefen M. A Multi-institutional Analysis of Perioperative Outcomes in 106 Men Who Underwent Radical Prostatectomy for Distant Metastatic Prostate Cancer at Presentation. Eur Urol. 2016 May;69(5):788-94. doi: 10.1016/j.eururo.2015.05.023. Epub 2015 May 30.

    PubMed 26038098

  • Gratzke C, Engel J, Stief CG. Role of radical prostatectomy in metastatic prostate cancer: data from the Munich Cancer Registry. Eur Urol. 2014 Sep;66(3):602-3. doi: 10.1016/j.eururo.2014.04.009. Epub 2014 May 10. No abstract available.

    PubMed 24821581

  • Leyh-Bannurah SR, Gazdovich S, Budaus L, Zaffuto E, Briganti A, Abdollah F, Montorsi F, Schiffmann J, Menon M, Shariat SF, Fisch M, Chun F, Steuber T, Huland H, Graefen M, Karakiewicz PI. Local Therapy Improves Survival in Metastatic Prostate Cancer. Eur Urol. 2017 Jul;72(1):118-124. doi: 10.1016/j.eururo.2017.03.020. Epub 2017 Apr 3.

    PubMed 28385454

  • Heidenreich A, Fossati N, Pfister D, Suardi N, Montorsi F, Shariat S, Grubmuller B, Gandaglia G, Briganti A, Karnes RJ. Cytoreductive Radical Prostatectomy in Men with Prostate Cancer and Skeletal Metastases. Eur Urol Oncol. 2018 May;1(1):46-53. doi: 10.1016/j.euo.2018.03.002. Epub 2018 May 15.

    PubMed 31100228

  • Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, Ritchie AWS, Attard G, Chowdhury S, Cross W, Dearnaley DP, Gillessen S, Gilson C, Jones RJ, Langley RE, Malik ZI, Mason MD, Matheson D, Millman R, Russell JM, Thalmann GN, Amos CL, Alonzi R, Bahl A, Birtle A, Din O, Douis H, Eswar C, Gale J, Gannon MR, Jonnada S, Khaksar S, Lester JF, O'Sullivan JM, Parikh OA, Pedley ID, Pudney DM, Sheehan DJ, Srihari NN, Tran ATH, Parmar MKB, Sydes MR; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018 Dec 1;392(10162):2353-2366. doi: 10.1016/S0140-6736(18)32486-3. Epub 2018 Oct 21.

    PubMed 30355464

  • Van den Broeck T, Oprea-Lager D, Moris L, Kailavasan M, Briers E, Cornford P, De Santis M, Gandaglia G, Gillessen Sommer S, Grummet JP, Grivas N, Lam TBL, Lardas M, Liew M, Mason M, O'Hanlon S, Pecanka J, Ploussard G, Rouviere O, Schoots IG, Tilki D, van den Bergh RCN, van der Poel H, Wiegel T, Willemse PP, Yuan CY, Mottet N. A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer. Eur Urol. 2021 Nov;80(5):531-545. doi: 10.1016/j.eururo.2021.04.028. Epub 2021 May 5.

    PubMed 33962808

Questions about this trial

What is this clinical trial studying?

A study testing APA + ADT and Local Treatmetn RT or RP in people with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC), run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 3 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Valentina Guadalupi, MD (00390223903811, valentina.guadalupi@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic Progression-Free Survival (rPFS) (time frame: Up to 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05649943, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025.

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