Clinical trial NCT06854250: Prostate Cryoablation Combined with Metronomic Cyclophosphamide for Metastatic Prostate Cancer
Official title: Androgen Deprivation Therapy Combined with Novel Androgen Receptor Inhibitors, Prostate Cryoablation, and Cyclophosphamide in the Treatment of Newly Diagnosed, Metastatic Prostate Cancer: a Single-Center, Single-Arm, Prospective Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Keywords: Metastatic prostate cancer
Novel androgen receptor inhibitors
Prostate cryoablation
Cyclophosphamide
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2025-03-03
Enrollment: 104
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to explore whether androgen deprivation therapy combined with novel androgen receptor inhibitors, prostate cryoablation, and metronomic cyclophosphamide is superior to the current treatment regimen of androgen deprivation therapy plus novel androgen receptor inhibitors for patients with metastatic prostate cancer. It will also learn about the safety of prostate cryoablation, and metronomic cyclophosphamide for patients with metastatic prostate cancer. The main questions it aims to answer are:

Does prostate cryoablation, and metronomic cyclophosphamide delay the progression of metastatic prostate cancer? Does prostate cryoablation, and metronomic cyclophosphamide reduce symptomatic local events of metastatic prostate cancer?

Researchers will explore if androgen deprivation therapy combined with novel androgen receptor inhibitors, prostate cryoablation, and metronomic cyclophosphamide works to treat metastatic prostate cancer.

Participants will:

Receive treatment of androgen deprivation therapy and novel androgen receptor inhibitors until progression.

Receive prostate cryoablation surgery and take cyclophosphamide. Visit the clinic every 1-3 months for checkups and tests. Keep a diary of their symptoms.

Detailed description: This study aims to evaluate the efficacy and safety of combining prostate cryoablation and cyclophosphamide with androgen deprivation therapy plus novel androgen receptor inhibitors (apalutamide, rezvilutamide, or darolutamide) in patients with newly diagnosed, metastatic prostate cancer. By comparing with previous studies, it seeks to explore whether prostate cryoablation and cyclophosphamide treatment can confer survival benefits and reduce symptomatic local urinary events in these patients.

Patients with newly diagnosed, metastatic prostate cancer who meet the inclusion criteria after evaluation will receive treatment with androgen deprivation therapy plus a novel androgen receptor inhibitor (apalutamide, rezvilutamide, or darolutamide) in combination with prostate cryoablation and cyclophosphamide. Enrolled patients should start the novel androgen receptor inhibitor (apalutamide, rezvilutamide, or darolutamide) within 3 months of initiating androgen deprivation therapy and undergo prostate cryoablation within 6 months of starting androgen deprivation therapy. Cyclophosphamide treatment will begin one day after prostate cryoablation and continue for a total of six months.

The primary endpoint of the study is PSA progression-free survival. Secondary endpoints include: 1) radiographic progression-free survival, 2) time to progression to metastatic castration-resistant prostate cancer, 3) overall survival, 4) PSA nadir, 5) incidence of symptomatic local events, and 6) safety.

Eligibility criteria: Inclusion Criteria:

* Males between 18 and 80 years old;
* Histopathological confirmation of prostatic acinar adenocarcinoma;
* Diagnosed with metastatic prostate cancer at initial diagnosis according to the AJCC 8th edition staging criteria;
* No progression at the time of initiating of prostate cryoablation;
* ECOG score of 0-1;
* Can tolerate general anesthesia and prostate cryoablation surgery;
* No significant abnormalities .
* Able to understand this study and sign the informed consent form.

Exclusion Criteria:

* Serious illness not suitable to receive the treatment regimen;
* Other malignant tumors (within 5 years), except for non-melanoma skin cancer;
* Receipt of treatments other than treatment regimen of this study;
* Prostate cancer invading the rectum;
* with prostate volumegreater than 55ml after 6 months of androgen deprivation therapy .

Primary outcomes:
measure: PSA progression-free survival
timeFrame: From date of initiation of androgen deprivation therapy until the date of PSA progression or date of death from any cause, whichever came first, assessed up to 5 years
Secondary outcomes:
measure: Radiographic progression-free survival
timeFrame: From date of initiation of androgen deprivation therapy until the date of radiographic progression or date of death from any cause, whichever came first, assessed up to 5 years
measure: mCRPC-free survival
timeFrame: From date of initiation of androgen deprivation therapy until the date of progression to metastatic castration-resistant prostate cancer or date of death from any cause, whichever came first, assessed up to 5 years
measure: Overall survival
timeFrame: From date of initiation of androgen deprivation therapy until the date of death from any cause, assessed up to 5 years
measure: Incidence of symptomatic local events
timeFrame: Through study completion, an average of 3 year
Other outcomes:
Locations:
Study officials:
References:
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citation: Li Y, Wang N, Zhao D, Wang J, Jiang L, Wang Y, Chen D, Wu Z, Zhou F, Yang Z. Cytoreductive prostate cryoablation and metronomic cyclophosphamide for metastatic hormone-sensitive prostate cancer. Future Oncol. 2022 Jun;18(19):2373-2380. doi: 10.2217/fon-2021-1424. Epub 2022 Apr 20.
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