Castration-Sensitive Prostate Cancer, Metastatic Prostate Cancer
Conditions
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.
Interventions
DRUGapalutamide
Patients receive apalutamide 240mg,qd,po.
DRUGandrogen deprivation therapy
Patients receive systemic ADT.
PROCEDUREcytoreductive radical prostatectomy with/without pelvic lymph node dissection
Patients receive cytoreductive radical prostatectomy with/without pelvic lymph node dissection.
RADIATIONmetastasis-directed therapy with radiation
Patients receive metastasis-directed therapy with radiation guided by post-treatment oligopersistent metastases.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 baseline | Baseline (Before trial treatment) | Imaging features before hormonal therapy |
| 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). |
| 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 treatment | At 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 |
| 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). |
Countries
China
Outcome results
None listed