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Maximal Cytoreductive Therapies on Post-treatment Metastases in Pts With mHSPC During Apalutamide Plus ADT Treatment

Phase 2
Not yet recruiting
Conditions
Castration-Sensitive Prostate Cancer
Metastatic Prostate Cancer
Interventions
Drug: androgen deprivation therapy
Procedure: cytoreductive radical prostatectomy with/without pelvic lymph node dissection
Radiation: metastasis-directed therapy with radiation
Registration Number
NCT05717582
Lead Sponsor
Fudan University
Brief Summary

To assess the feasibility and safety of Maximal cytoreductive therapies in patients with de novo mCSPC who achieve ≤10 oligopersistent metastases on PSMA PET CT after initial 3-month systemic treatment with apalutamide plus ADT. Maximal cytoreductive therapies consist of 1.cytoreductive radical prostatectomy with/without PLND guided by post-treatment PET 2.metastasis-directed therapy with radiation guided by post-treatment oligopersistent metastases. All patients receive continuous systemic treatment with apalutamide plus ADT.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Male
Target Recruitment
47
Inclusion Criteria
  1. Able to understand and willing to sign the informed consent;
  2. Aged ≥18 years;
  3. Histologically or cytologically confirmed prostate adenocarcinoma (primary small cell carcinoma or signet-ring cell carcinoma of the prostate are not allowed, however adenocarcinoma with neuroendocrine differentiation accounting ≤10% is allowed);
  4. Newly diagnosed prostate cancer (within 3 months prior to enrollment);
  5. M1a/b disease with the presence of 1-10 visible metastases at diagnosis by conventional imagine including bone scan (ECT) and CT or MRI of the chest, abdomen, and pelvis;
  6. With initial systemic treatment of apalutamide plus ADT and willing and expected to comply with treatment and follow up schedule [No more than 2-month systemic treatment before enrollment (including ADT and ADT combined with short-term first-generation anti-androgen therapy (flutamide or bicalutamide); To maximize enrollment, patients who had started apalutamide plus ADT before enrollment are allowed into the study provided that they are otherwise eligible and therapy was initiated no longer than 2 months before enrollment];
  7. Fit to undergo cytoreductive radical prostatectomy and radiotherapy to the visible sites of metastases;
  8. ECOG PS score is 0-1;
  9. Adequate organ function;
  10. Life expectancy ≥ 12 months.
Exclusion Criteria
  1. History of allergies, hypersensitivity, or intolerance to any drug used in the study;

  2. Had the contraindications or is intolerant to cRP or RT;

  3. Had any visceral metastases (brain, liver, lung etc.) on screening conventional imaging (bone scans, CT or MRI);

  4. Prior Received any of the following treatments for primary and metastatic prostate cancer;

    1. >2-month ADT or first-generation antiandrogens (bicalutamide, flutamide etc.);
    2. Any other novel hormonal therapies (enzalutamide, darolutamide, abiraterone etc.) except ≤ 2-month apalutamide plus ADT listed in inclusion criteria;
    3. Any chemotherapy;
    4. local treatment or metastatic treatment for primary prostate cancer or metastases;
    5. Any immunotherapy (PD-L1 etc.), target therapy (PARPi etc), etc;
  5. History of seizure or known condition that may predispose to seizure;

  6. History of major surgery 4 weeks before enrollment;

  7. Had major cardiovascular and cerebrovascular diseases within 6 months prior to the start of the study;

  8. Any condition that could interfere with drug absorption(e.g. unable to swallow, chronic diarrhea etc. );

  9. Conditions of active infection;

  10. History of previous or current malignant disease, except for curatively treated tumors cured for more than 3 years;

  11. Patients who is currently undergoing other trials;

  12. Unwilling or difficult to cooperate with treatment and follow-up visit;

  13. Other sever conditions which could interfere with trial safety or results judged by the investigator.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
maximal-cytoreductive therapyandrogen deprivation therapyPatients with de novo mCSPC who achieve ≤10 oligopersistent metastases on PSMA PET CT after initial 3-month systemic treatment with apalutamide plus ADT will receive cytoreductive radical prostatectomy with/without PLND and metastasis-directed therapy with radiation.
maximal-cytoreductive therapymetastasis-directed therapy with radiationPatients with de novo mCSPC who achieve ≤10 oligopersistent metastases on PSMA PET CT after initial 3-month systemic treatment with apalutamide plus ADT will receive cytoreductive radical prostatectomy with/without PLND and metastasis-directed therapy with radiation.
maximal-cytoreductive therapycytoreductive radical prostatectomy with/without pelvic lymph node dissectionPatients with de novo mCSPC who achieve ≤10 oligopersistent metastases on PSMA PET CT after initial 3-month systemic treatment with apalutamide plus ADT will receive cytoreductive radical prostatectomy with/without PLND and metastasis-directed therapy with radiation.
maximal-cytoreductive therapyapalutamidePatients with de novo mCSPC who achieve ≤10 oligopersistent metastases on PSMA PET CT after initial 3-month systemic treatment with apalutamide plus ADT will receive cytoreductive radical prostatectomy with/without PLND and metastasis-directed therapy with radiation.
Primary Outcome Measures
NameTimeMethod
proportion of patients with undetectable PSA level after 6 cycles of treatment (each cycle is 28 days).At the end of the 6th cycle of treatment (each cycle is 28 days).

It is defined as the proportion of patients with PSA≤0.2 ng/mL without disease progression or symptomatic deterioration after 6 cycles of study treatment (each cycle is 28 days).

Secondary Outcome Measures
NameTimeMethod
proportion of patients with undetectable PSA level after 3 cycles of treatment (each cycle is 28 days).At the end of the 3rd cycle of treatment (each cycle is 28 days).

It is defined as the proportion of patients with PSA≤0.2 ng/mL after 3 cycles of study treatment (each cycle is 28 days).

PSA50 response rate and PSA90 response rate at the end of the 6th treatment cycle (each cycle is 28 days).At the end of the 6th cycle of treatment (each cycle is 28 days).

It is defined as the proportion of patients with a PSA reduction of over 50% / 90%compared with baseline.

Conventional imaging and PSMA-PET/CT imaging features at baselineBaseline (Before trial treatment)

Imaging features before hormonal therapy

Proportion of patients with ≤ 10 metastases on PSMA-PET/CT imaging at the end of the third treatment cycle (each cycle is 28 days).At the end of the 3rd cycle of treatment (each cycle is 28 days).

Proportion of patients with ≤ 10 metastases on PSMA-PET/CT imaging at the end of the third treatment cycle (each cycle is 28 days).

PSA50 response rate and PSA90 response rate at the end of the 3rd treatment cycle (each cycle is 28 days).At the end of the 3rd cycle of treatment (each cycle is 28 days).

It is defined as the proportion of patients with a PSA reduction of over 50% / 90%compared with baseline.

Comparison of imaging features between conventional imaging and PSMA PET/CT.At the end of the 3rd and 6th cycle of treatment (each cycle is 28 days).

Including prostate volume, tumor burden, distribution of metastatic lesions etc.

Feasibility and safety of performing cRP±MDT treatmentAt the end of the 6th cycle of treatment (each cycle is 28 days).

Feasibility and safety of performing cRP±MDT guided by oligopersistent metastases assessed by PSMA PET/CT

Trial Locations

Locations (2)

Fudan University Shanghai Cancer Center Pudong Hospital

🇨🇳

Shanghai, Shanghai, China

Fudan University Shanghai Cancer Center Xuhui Hospital

🇨🇳

Shanghai, Shanghai, China

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