Carboplatin Chemotherapy Before Surgery for People With High-Risk Prostate Cancer and an Inherited BRCA1 or BRCA2 Gene Mutation

Phase 2

Recruiting

• Conditions: Stage IIIB Prostate Cancer AJCC v8; Prostate Adenocarcinoma; Stage IIIC Prostate Cancer AJCC v8
• Interventions: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Chest Radiography; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: PSMA PET Scan; Procedure: Surgical Procedure

• Registration Number: NCT05806515
• Lead Sponsor: SWOG Cancer Research Network

Brief Summary

This phase II trial tests how well carboplatin before surgery works in treating patients with high-risk prostate cancer and an inherited BRCA1 or BRCA2 gene mutation. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping, or slowing the growth of tumor cells. Giving carboplatin before surgery may shrink tumors in patients with high-risk prostate cancer with BRCA1 and BRCA2 gene mutations.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the pathologic complete response rate at prostatectomy in patients with localized high-risk prostate cancer with germline BRCA2 or BRCA1 mutations who are treated with neoadjuvant carboplatin by central review of source documents.

SECONDARY OBJECTIVES:

I. To evaluate prostate specific antigen (PSA) progression-free survival post-prostatectomy over the duration of follow-up and specifically, at the 3-year landmark.

II. To evaluate metastases free survival and overall survival. III. To evaluate the frequency and severity of toxicities of neoadjuvant carboplatin followed by radical prostatectomy.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE:

Patients receive carboplatin intravenously (IV) on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis, CT of the chest or chest X-ray, or prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) throughout the trial. Patients also undergo collection of blood samples throughout the trial.

Study Timeline

• Study First Submitted: 2023-03-28
• Study First Submitted QC: 2023-03-28
• Study First Posted: 2023-04-10
• Study Start: 2024-03-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-05
• Last Update Posted: 2024-07-08
• Primary Completion: 2026-07
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 44

Inclusion Criteria

• Participant must have histologic diagnosis of prostate adenocarcinoma

• Participant must have high or very high-risk disease defined by at least one of the following:

  • cT3a - cT4x
  • Grade group 4 or 5 (Gleason sum 8-10)
  • PSA > 20 ng/mL prior to registration

• Participant must have documented evidence of germline mutation (pathogenic/likely pathogenic variant) in BRCA2 or BRCA1 through testing in a Clinical Laboratory Improvement Act (CLIA)-certified lab

  • NOTE: Local lab report is sufficient for eligibility

• Participant may have initiated gonadotrophin releasing hormone (gnRH) agonist, gnRH antagonist, oral anti-androgen (e.g. bicalutamide, nilutamide, flutamide), or other agent intended to treat prostate cancer prior to registration. The effectiveness of the current depot of such treatment must not extend beyond 1 month after study registration. Agents listed above cannot be started after participant registration

• Participant must be >= 18 years old

• Participant must have Zubrod performance status of 0-2

• Participant must have a complete medical history and physical exam within 28 days prior to registration

• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)

• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to registration)

• Participant must have a serum creatinine =< the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration

• Participant must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification within 28 days prior to registration. To be eligible for this trial, participants must be class 2B or better

• Participant with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to registration

• Participant with history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within in 28 days prior to registration

• Participant with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within in 28 days prior to registration

• Participants who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including vasectomy with testing showing no sperm in the semen

• Prior to registration, participant must have had a urologic consult and be deemed a surgical candidate with known sites of disease deemed by the urologist to be potentially resectable

• Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System

• NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
  • As part of the registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Exclusion Criteria

• Participant must not have evidence of distant metastatic disease by conventional imaging within 90 days prior to registration

  • NOTE: cN1 detected only by PSMA-PET is permitted if urologist deems sites of disease to be potentially completely resectable

• Participant must not have received prior radiation therapy (RT) to the pelvic region

• Participant must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of protocol treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (carboplatin)	PSMA PET Scan	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Treatment (carboplatin)	Biospecimen Collection	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Treatment (carboplatin)	Chest Radiography	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Treatment (carboplatin)	Computed Tomography	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Treatment (carboplatin)	Magnetic Resonance Imaging	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Treatment (carboplatin)	Surgical Procedure	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Treatment (carboplatin)	Carboplatin	Patients receive carboplatin IV on study. Patients then undergo surgery on study. Patients who experience PSA progression after surgery undergo CT or MRI of the abdomen and pelvis, CT of the chest or chest X-ray, or PSMA-PET throughout the trial. Patients also undergo collection of blood samples throughout the trial.

Primary Outcome Measures

Name	Time	Method
Pathologic complete response after neoadjuvant carboplatin	Up to 5 years	A two-stage design will be used.

Trial Locations

Locations (133)

Mercy Cancer Center �� Carmichael; 🇺🇸 Carmichael, California, United States

Mercy San Juan Medical Center; 🇺🇸 Carmichael, California, United States

City of Hope at Irvine Lennar; 🇺🇸 Irvine, California, United States

Saint Alphonsus Cancer Care Center-Boise; 🇺🇸 Boise, Idaho, United States

Saint Patrick Hospital - Community Hospital; 🇺🇸 Missoula, Montana, United States

Saint Elizabeth Regional Medical Center; 🇺🇸 Lincoln, Nebraska, United States

Saint Luke's Cancer Institute - Nampa; 🇺🇸 Nampa, Idaho, United States

NorthShore University HealthSystem-Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

North Shore Medical Center; 🇺🇸 Skokie, Illinois, United States

Benefis Healthcare- Sletten Cancer Institute; 🇺🇸 Great Falls, Montana, United States

NorthShore University HealthSystem-Glenbrook Hospital; 🇺🇸 Glenview, Illinois, United States

Kalispell Regional Medical Center; 🇺🇸 Kalispell, Montana, United States

Flaget Memorial Hospital; 🇺🇸 Bardstown, Kentucky, United States

Clackamas Radiation Oncology Center; 🇺🇸 Clackamas, Oregon, United States

Providence Cancer Institute Clackamas Clinic; 🇺🇸 Clackamas, Oregon, United States

Providence Newberg Medical Center; 🇺🇸 Newberg, Oregon, United States

Swedish Cancer Institute-Edmonds; 🇺🇸 Edmonds, Washington, United States

FHCC South Lake Union; 🇺🇸 Seattle, Washington, United States

Swedish Medical Center-Cherry Hill; 🇺🇸 Seattle, Washington, United States

Swedish Medical Center-First Hill; 🇺🇸 Seattle, Washington, United States

Good Samaritan Hospital - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Bethesda North Hospital; 🇺🇸 Cincinnati, Ohio, United States

TriHealth Cancer Institute-Westside; 🇺🇸 Cincinnati, Ohio, United States

TriHealth Cancer Institute-Anderson; 🇺🇸 Cincinnati, Ohio, United States

Billings Clinic-Cody; 🇺🇸 Cody, Wyoming, United States

Porter Adventist Hospital; 🇺🇸 Denver, Colorado, United States

Alegent Health Immanuel Medical Center; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Bergan Mercy Medical Center; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Lakeside Hospital; 🇺🇸 Omaha, Nebraska, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Katmai Oncology Group; 🇺🇸 Anchorage, Alaska, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Mercy Cancer Center - Elk Grove; 🇺🇸 Elk Grove, California, United States

Mercy Medical Center; 🇺🇸 Durango, Colorado, United States

Providence Medical Foundation - Santa Rosa; 🇺🇸 Santa Rosa, California, United States

Pacific Central Coast Health Center-San Luis Obispo; 🇺🇸 San Luis Obispo, California, United States

Woodland Memorial Hospital; 🇺🇸 Woodland, California, United States

Penrose-Saint Francis Healthcare; 🇺🇸 Colorado Springs, Colorado, United States

Littleton Adventist Hospital; 🇺🇸 Littleton, Colorado, United States

Smilow Cancer Hospital-Derby Care Center; 🇺🇸 Derby, Connecticut, United States

Smilow Cancer Hospital Care Center at Long Ridge; 🇺🇸 Stamford, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich; 🇺🇸 Greenwich, Connecticut, United States

Smilow Cancer Hospital-Torrington Care Center; 🇺🇸 Torrington, Connecticut, United States

Idaho Urologic Institute-Meridian; 🇺🇸 Meridian, Idaho, United States

Saint Joseph Hospital East; 🇺🇸 Lexington, Kentucky, United States

Saint Joseph London; 🇺🇸 London, Kentucky, United States

Swedish Medical Center-Ballard Campus; 🇺🇸 Seattle, Washington, United States

PeaceHealth Saint Joseph Medical Center; 🇺🇸 Bellingham, Washington, United States

Southwest Oncology PC; 🇺🇸 Durango, Colorado, United States

Saint Anthony Hospital; 🇺🇸 Lakewood, Colorado, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Anchorage Radiation Therapy Center; 🇺🇸 Anchorage, Alaska, United States

Alaska Women's Cancer Care; 🇺🇸 Anchorage, Alaska, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Mission Hope Medical Oncology - Arroyo Grande; 🇺🇸 Arroyo Grande, California, United States

Mission Hope Medical Oncology - Santa Maria; 🇺🇸 Santa Maria, California, United States

Providence Queen of The Valley; 🇺🇸 Napa, California, United States

Mercy Cancer Center - Rocklin; 🇺🇸 Rocklin, California, United States

Providence Santa Rosa Memorial Hospital; 🇺🇸 Santa Rosa, California, United States

Saint Francis Cancer Center; 🇺🇸 Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose; 🇺🇸 Colorado Springs, Colorado, United States

Yale-New Haven Hospital North Haven Medical Center; 🇺🇸 North Haven, Connecticut, United States

Longmont United Hospital; 🇺🇸 Longmont, Colorado, United States

Smilow Cancer Hospital Care Center - Guilford; 🇺🇸 Guilford, Connecticut, United States

Saint Mary Corwin Medical Center; 🇺🇸 Pueblo, Colorado, United States

Smilow Cancer Hospital Care Center-Fairfield; 🇺🇸 Fairfield, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center; 🇺🇸 Waterbury, Connecticut, United States

Saint Luke's Cancer Institute - Boise; 🇺🇸 Boise, Idaho, United States

Saint Alphonsus Cancer Care Center-Caldwell; 🇺🇸 Caldwell, Idaho, United States

Saint Luke's Cancer Institute - Fruitland; 🇺🇸 Fruitland, Idaho, United States

Kootenai Health - Coeur d'Alene; 🇺🇸 Coeur d'Alene, Idaho, United States

Walter Knox Memorial Hospital; 🇺🇸 Emmett, Idaho, United States

Kootenai Clinic Cancer Services - Post Falls; 🇺🇸 Post Falls, Idaho, United States

Kootenai Cancer Clinic; 🇺🇸 Sandpoint, Idaho, United States

Saint Luke's Cancer Institute - Twin Falls; 🇺🇸 Twin Falls, Idaho, United States

NorthShore University HealthSystem-Highland Park Hospital; 🇺🇸 Highland Park, Illinois, United States

Alegent Health Mercy Hospital; 🇺🇸 Council Bluffs, Iowa, United States

Saint Joseph Hospital; 🇺🇸 Lexington, Kentucky, United States

Commonwealth Cancer Center-Corbin; 🇺🇸 Corbin, Kentucky, United States

Saint Joseph Radiation Oncology Resource Center; 🇺🇸 Lexington, Kentucky, United States

Billings Clinic Cancer Center; 🇺🇸 Billings, Montana, United States

Saint Joseph Mount Sterling; 🇺🇸 Mount Sterling, Kentucky, United States

LSU Healthcare Network / Metairie Multi-Specialty Clinic; 🇺🇸 Metairie, Louisiana, United States

CHI Health Good Samaritan; 🇺🇸 Kearney, Nebraska, United States

Midlands Community Hospital; 🇺🇸 Papillion, Nebraska, United States

Garnet Health Medical Center; 🇺🇸 Middletown, New York, United States

Saint Alphonsus Medical Center-Baker City; 🇺🇸 Baker City, Oregon, United States

Saint Charles Health System; 🇺🇸 Bend, Oregon, United States

Bay Area Hospital; 🇺🇸 Coos Bay, Oregon, United States

Saint Alphonsus Medical Center-Ontario; 🇺🇸 Ontario, Oregon, United States

Providence Willamette Falls Medical Center; 🇺🇸 Oregon City, Oregon, United States

Saint Charles Health System-Redmond; 🇺🇸 Redmond, Oregon, United States

Providence Saint Vincent Medical Center; 🇺🇸 Portland, Oregon, United States

Providence Regional Cancer System-Aberdeen; 🇺🇸 Aberdeen, Washington, United States

Smilow Cancer Hospital Care Center - Westerly; 🇺🇸 Westerly, Rhode Island, United States

Providence Regional Cancer System-Centralia; 🇺🇸 Centralia, Washington, United States

Harrison Medical Center; 🇺🇸 Bremerton, Washington, United States

Providence Regional Cancer Partnership; 🇺🇸 Everett, Washington, United States

Kadlec Clinic Hematology and Oncology; 🇺🇸 Kennewick, Washington, United States

Swedish Cancer Institute-Issaquah; 🇺🇸 Issaquah, Washington, United States

Providence Regional Cancer System-Lacey; 🇺🇸 Lacey, Washington, United States

PeaceHealth Saint John Medical Center; 🇺🇸 Longview, Washington, United States

University of Washington Medical Center - Montlake; 🇺🇸 Seattle, Washington, United States

Providence Saint Mary Regional Cancer Center; 🇺🇸 Walla Walla, Washington, United States

PeaceHealth Southwest Medical Center; 🇺🇸 Vancouver, Washington, United States

PeaceHealth United General Medical Center; 🇺🇸 Sedro-Woolley, Washington, United States

Providence Regional Cancer System-Shelton; 🇺🇸 Shelton, Washington, United States

Providence Regional Cancer System-Yelm; 🇺🇸 Yelm, Washington, United States

Alaska Breast Care and Surgery LLC; 🇺🇸 Anchorage, Alaska, United States

Anchorage Associates in Radiation Medicine; 🇺🇸 Anchorage, Alaska, United States

Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC; 🇺🇸 Anchorage, Alaska, United States

Anchorage Oncology Centre; 🇺🇸 Anchorage, Alaska, United States

Cancer Center at Saint Joseph's; 🇺🇸 Phoenix, Arizona, United States

Smilow Cancer Hospital Care Center at Saint Francis; 🇺🇸 Hartford, Connecticut, United States

Saint Alphonsus Cancer Care Center-Nampa; 🇺🇸 Nampa, Idaho, United States

Community Medical Hospital; 🇺🇸 Missoula, Montana, United States

Smilow Cancer Hospital Care Center at Glastonbury; 🇺🇸 Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford; 🇺🇸 Waterford, Connecticut, United States

Saint Luke's Cancer Institute - Meridian; 🇺🇸 Meridian, Idaho, United States

Bozeman Deaconess Hospital; 🇺🇸 Bozeman, Montana, United States

Great Falls Clinic; 🇺🇸 Great Falls, Montana, United States

Community Hospital of Anaconda; 🇺🇸 Anaconda, Montana, United States

Creighton University Medical Center; 🇺🇸 Omaha, Nebraska, United States

Mercy Cancer Center - Sacramento; 🇺🇸 Sacramento, California, United States

Smilow Cancer Center/Yale-New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

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

Louisiana State University Health Science Center; 🇺🇸 New Orleans, Louisiana, United States

Parker Adventist Hospital; 🇺🇸 Parker, Colorado, United States

Smilow Cancer Hospital Care Center-Trumbull; 🇺🇸 Trumbull, Connecticut, United States

Welch Cancer Center; 🇺🇸 Sheridan, Wyoming, United States