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

Overview

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.

Interventions

• Procedure Prostate cryoablation
  Enrolled patients will receive prostate cryoablation within 6 months of starting androgen deprivation therapy.
• Drug Cyclophosphamide (CTX)
  Enrolled patients will receive cyclophosphamide (50mg daily) one day after prostate cryoablation and continue for a total of six months.

Primary outcome measures

• PSA progression-free survival [Time frame: 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 outcome measures (4)

• Radiographic progression-free survival [Time frame: 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]
• mCRPC-free survival [Time frame: 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]
• Overall survival [Time frame: From date of initiation of androgen deprivation therapy until the date of death from any cause, assessed up to 5 years]
• Incidence of symptomatic local events [Time frame: Through study completion, an average of 3 year]

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 .

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Publications

• Si T, Guo Z, Hao X. Combined cryoablation and GM-CSF treatment for metastatic hormone refractory prostate cancer. J Immunother. 2009 Jan;32(1):86-91. doi: 10.1097/CJI.0b013e31818df785. PMID 19307997
• Donnelly BJ, Saliken JC, Brasher PM, Ernst SD, Rewcastle JC, Lau H, Robinson J, Trpkov K. A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer. Cancer. 2010 Jan 15;116(2):323-30. doi: 10.1002/cncr.24779. PMID 19937954
• Shah TT, Peters M, Eldred-Evans D, Miah S, Yap T, Faure-Walker NA, Hosking-Jervis F, Thomas B, Dudderidge T, Hindley RG, McCracken S, Greene D, Nigam R, Valerio M, Minhas S, Winkler M, Arya M, Ahmed HU. Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry. Eur Urol. 2019 Jul;76(1):98-105. doi: PMID 30638633
• Tsuboi I, Matsukawa A, Kardoust Parizi M, Klemm J, Mancon S, Chiujdea S, Fazekas T, Miszczyk M, Laukhtina E, Kawada T, Katayama S, Iwata T, Bekku K, Karakiewicz P, Wada K, Roupret M, Araki M, Shariat SF. A Systematic Review and Meta-analysis of the Impact of Local Therapies on Local Event Suppression in Metastatic Hormone-sensitive Prostate Cancer. Eur Urol Oncol. 2024 Dec;7(6):1185-1194. doi: 10. PMID 38575408
• 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. PMID 35440168
• Wang N, Ye Y, Deng M, Zhao D, Jiang L, Chen D, Wu Z, Wang Y, Li Z, Yang Z, Li J, Zhou F, Li Y. Prostate cryoablation combined with androgen deprivation therapy for newly diagnosed metastatic prostate cancer: a propensity score-based study. Prostate Cancer Prostatic Dis. 2021 Sep;24(3):837-844. doi: 10.1038/s41391-021-00335-2. Epub 2021 Mar 4. PMID 33664457

Identifiers

NCT: NCT06854250 · 2024-FXY-295 · SL-B2024-623-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗