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

Stage IV Prostate Adenocarcinoma AJCC v7 Clinical Trial

Official title:

SIMCAP (Surgery in Metastatic Carcinoma of Prostate): Phase 2.5 Multi-Institution Randomized Prospective Clinical Trial Evaluating the Impact of Cytoreductive Radical Prostatectomy Combined With Best Systemic Therapy on Oncologic and Quality of Life Outcomes in Men With Newly Diagnosed Metastatic Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03456843
• Other study ID #: 2000031290
• Secondary ID: NCI-2018-0004708
• Status: Recruiting
• Phase: Phase 2
• Start date: March 14, 2018
• Est. completion date: October 31, 2024

Study information

• Verified date: January 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Stage IV Prostate Adenocarcinoma AJCC v7

Intervention

Drug:
• Antiandrogen Therapy
To demonstrate at least 30% improvement in FFS at 2 years after randomization with the power of 90% and error of 5% on a one-sided exponential MLE test.
• Docetaxel
To demonstrate at least 30% improvement in FFS at 2 years after randomization with the power of 90% and error of 5% on a one-sided exponential MLE test.

Other:
• Laboratory Biomarker Analysis
Correlative studies

Procedure:
• Quality-of-Life Assessment
Ancillary studies

Other:
• Questionnaire Administration
Ancillary studies

Procedure:
• Radical Prostatectomy
Undergo cytoreductive radical prostatectomy

Locations

Country	Name	City	State
Australia	Epworth Healthcare	East Melbourne
China	Chinese University of Hong Kong	Hong Kong
Japan	Akita University	Akita
Japan	Kindai University	Osaka-sayama	Osaka
Japan	Kyoto University	Sako	Kyoto
Japan	Juntendo University	Tokyo
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Taiwan	National Taiwan University Hospital	Taipei
United States	University of Chicago	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	University of California	Irvine	California
United States	University of Southern California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Unniversity of Pennsylvania	Philadelphia	Pennsylvania
United States	Swedish Medical Services	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  China,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival (FFS)	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.	At 2 years
Secondary	Cancer-specific survival		Up to 2 years
Secondary	Overall complication rate		Up to 2 years
Secondary	Time to biochemical progression		Up to 2 years
Secondary	Overall survival		Through study completion, a minimum of 4 years