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

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective Study of Maximal-Cytoreductive Therapies for Patients With de Novo Metastatic Hormone-sensitive Prostate Cancer Who Achieve Oligopersistent Metastases During Systemic Treatment With Apalutamide Plus ADT (CHAMPION Study)

Conditions
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Metastatic Prostate Cancer, Castration-Sensitive Prostate Cancer

Intervention / Treatment
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* Drug: apalutamide
* Drug: androgen deprivation therapy
* Procedure: cytoreductive radical prostatectomy with/without pelvic lymph node dissection
* Radiation: metastasis-directed therapy with radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and willing to sign the informed consent; Aged ≥18 years; 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); Newly diagnosed prostate cancer (within 3 months prior to enrollment); 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; 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]; Fit to undergo cytoreductive radical prostatectomy and radiotherapy to the visible sites of metastases; ECOG PS score is 0-1; Adequate organ function; Life expectancy ≥ 12 months. Exclusion Criteria: History of allergies, hypersensitivity, or intolerance to any drug used in the study; Had the contraindications or is intolerant to cRP or RT; Had any visceral metastases (brain, liver, lung etc.) on screening conventional imaging (bone scans, CT or MRI); Prior Received any of the following treatments for primary and metastatic prostate cancer; >2-month ADT or first-generation antiandrogens (bicalutamide, flutamide etc.); Any other novel hormonal therapies (enzalutamide, darolutamide, abiraterone etc.) except ≤ 2-month apalutamide plus ADT listed in inclusion criteria; Any chemotherapy; local treatment or metastatic treatment for primary prostate cancer or metastases; Any immunotherapy (PD-L1 etc.), target therapy (PARPi etc), etc; History of seizure or known condition that may predispose to seizure; History of major surgery 4 weeks before enrollment; Had major cardiovascular and cerebrovascular diseases within 6 months prior to the start of the study; Any condition that could interfere with drug absorption(e.g. unable to swallow, chronic diarrhea etc. ); Conditions of active infection; History of previous or current malignant disease, except for curatively treated tumors cured for more than 3 years; Patients who is currently undergoing other trials; Unwilling or difficult to cooperate with treatment and follow-up visit; Other sever conditions which could interfere with trial safety or results judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: maximal-cytoreductive therapy<br>Patients 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. | Drug: apalutamide<br>* Patients receive apalutamide 240mg,qd,po.<br>Drug: androgen deprivation therapy<br>* Patients receive systemic ADT.<br>Procedure: cytoreductive radical prostatectomy with/without pelvic lymph node dissection<br>* Patients receive cytoreductive radical prostatectomy with/without pelvic lymph node dissection.<br>Radiation: metastasis-directed therapy with radiation<br>* Patients receive metastasis-directed therapy with radiation guided by post-treatment oligopersistent metastases.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with undetectable PSA level after 6 cycles 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). | At the end of the 6th cycle of treatment (each cycle is 28 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with undetectable PSA level after 3 cycles 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). | At the end of the 3rd cycle of treatment (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). | It is defined as the proportion of patients with a PSA reduction of over 50% / 90%compared with baseline. | At the end of the 3rd cycle of 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). | It is defined as the proportion of patients with a PSA reduction of over 50% / 90%compared with baseline. | At the end of the 6th cycle of treatment (each cycle is 28 days). | 
| Conventional imaging and PSMA-PET/CT imaging features at baseline | Imaging features before hormonal therapy | Baseline (Before trial treatment) | 
| Proportion of patients with ≤ 10 metastases on PSMA-PET/CT imaging at the end of the third treatment cycle (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). | At the end of the 3rd cycle of treatment (each cycle is 28 days). | 
| Comparison of imaging features between conventional imaging and PSMA PET/CT. | Including prostate volume, tumor burden, distribution of metastatic lesions etc. | At the end of the 3rd and 6th cycle of treatment (each cycle is 28 days). | 
| Feasibility and safety of performing cRP±MDT treatment | Feasibility and safety of performing cRP±MDT guided by oligopersistent metastases assessed by PSMA PET/CT | At the end of the 6th cycle of treatment (each cycle is 28 days). |