Therapeutic Effect of Cytoreductive Radical Prostatectomy in Men With Newly Diagnosed Metastatic Prostate Cancer

Phase 2

Recruiting

• Conditions: Stage IV Prostate Adenocarcinoma AJCC v7
• Interventions: Drug: Antiandrogen Therapy; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Radical Prostatectomy

• Registration Number: NCT03456843
• Lead Sponsor: Yale University

Brief Summary

This randomized phase II trial studies how well surgical removal of the prostate and antiandrogen therapy with or without docetaxel work in treating men with newly diagnosed prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Antiandrogen therapy may lessen the amount of androgens made by the body. Drugs used in chemotherapy, such as docetaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Surgery, antiandrogen therapy and docetaxel may work better in treating participants with prostate cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the clinical benefit of combining radical surgery cytoreductive radical prostatectomy (CRP) - with the best systemic therapy (BST) in men with newly diagnosed clinical metastatic prostate cancer (mPCa).

SECONDARY OBJECTIVES:

I. To determine the impact of CRP+BST on time to biochemical progression, cancer-specific survival, complication rates, and quality of life (QOL) in patients with mPCa.

II. To determine the transcription levels of bone morphogenetic protein -6 (BMP-6) and transforming growth factor-beta (TGF-?).

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.

ARM II: Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 6 months from time of progression.

Study Timeline

• Study First Submitted: 2018-02-20
• Study First Submitted QC: 2018-02-28
• Study First Posted: 2018-03-07
• Study Start: 2018-03-14
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-25
• Primary Completion: 2027-03
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 190

Inclusion Criteria

• Histologically proven adenocarcinoma of the prostate
• Evidence of metastasis by magnetic resonance imaging (MRI)/computed tomography (CT) scan, bone scan, or histologic confirmation
• Clinical stage M1a (distant lymph node positive), M1b (bone metastasis), or M1c (solid organ metastasis.
• If solitary lesion, metastasis confirmed with either biopsy or two independent imaging modalities (i.e. CT and PET [positron emission tomography], bone scan and MRI, modality at the discretion of the treating physician)
• No previous local therapy for prostate cancer (i.e prostate radiation, cryotherapy, etc.)
• Give informed consent
• Prostate deemed resectable by surgeon
• Plans to start or has already started antiandrogen therapy (ADT) no longer than 6 months prior to consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Hemoglobin (HgB) >= 9 g/dL compatible for surgery
• Platelets > 80,000/mcL compatible for surgery
• Aspartate aminotransferase (AST) =< 2x upper limit of normal (ULN) compatible for surgery
• Alanine aminotransferase (ALT) =< 2x upper limit of normal (ULN) compatible for surgery

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Exclusion Criteria

• Refuses to give informed consent
• Deemed to have unresectable disease by surgeon
• Received ADT for more than 6 months prior to consent
• Life expectancy of less than 6 months prior to consent
• Active spinal cord compression
• Deep vein thrombosis (DVT) / pulmonary embolism (PE) in the past 6 months prior to consent
• Previous local therapy for prostate cancer
• Patients who have chemotherapy or radiotherapy for non-prostate cancer related treatment within 3 weeks prior to consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (ADT, docetaxel)	Antiandrogen Therapy	Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Arm I (ADT, docetaxel)	Laboratory Biomarker Analysis	Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Arm I (ADT, docetaxel)	Quality-of-Life Assessment	Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Arm I (ADT, docetaxel)	Questionnaire Administration	Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Arm II (ADT, radical prostatectomy, docetaxel)	Antiandrogen Therapy	Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.
Arm II (ADT, radical prostatectomy, docetaxel)	Questionnaire Administration	Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.
Arm II (ADT, radical prostatectomy, docetaxel)	Radical Prostatectomy	Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.
Arm II (ADT, radical prostatectomy, docetaxel)	Laboratory Biomarker Analysis	Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.
Arm II (ADT, radical prostatectomy, docetaxel)	Quality-of-Life Assessment	Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.
Arm I (ADT, docetaxel)	Docetaxel	Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Arm II (ADT, radical prostatectomy, docetaxel)	Docetaxel	Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician.

Primary Outcome Measures

Name	Time	Method
Failure-free survival (FFS)	At 2 years	Failure is defined as any one of the following events: PSA progression, clinical progression, radiographic progression, or death from prostate cancer. The % of men who fail within 2 years of randomization will be compare between the two groups using a one-sided log-rank test.

Secondary Outcome Measures

Name	Time	Method
Cancer-specific survival	Up to 2 years
Overall complication rate	Up to 2 years
Time to biochemical progression	Up to 2 years
Overall survival	Through study completion, a minimum of 4 years

Trial Locations

Locations (20)

Samsung Medical Center; 🇰🇷 Gangnam-gu, Seoul, Korea, Republic of

City of Hope; 🇺🇸 Duarte, California, United States

University of California; 🇺🇸 Irvine, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Unniversity of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

Swedish Medical Services; 🇺🇸 Seattle, Washington, United States

Epworth Healthcare; 🇦🇺 East Melbourne, Australia

Chinese University of Hong Kong; 🇨🇳 Hong Kong, China

Kyoto University; 🇯🇵 Sako, Kyoto, Japan

Kindai University; 🇯🇵 Ōsaka-sayama, Osaka, Japan

Akita University; 🇯🇵 Akita, Japan

Juntendo University; 🇯🇵 Tokyo, Japan

National Cancer Center; 🇰🇷 Goyang-si, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Gyeonggi-do, Korea, Republic of

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan