PREcision DIagnostics in Prostate Cancer Treatment (PREDICT)
Overview
- Phase
- Phase 2
- Intervention
- PSMA PET Scan
- Conditions
- Castration-Resistant Prostate Carcinoma
- Sponsor
- Alliance for Clinical Trials in Oncology
- Enrollment
- 474
- Locations
- 179
- Primary Endpoint
- Objective Response
- Status
- Recruiting
- Last Updated
- 25 days ago
Overview
Brief Summary
This phase II trial evaluates whether genetic testing in prostate cancer is helpful in deciding which study treatment patients are assigned. Patient cancer tissue samples are obtained from a previous surgery or biopsy procedure and tested for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) abnormalities or mutations in their cancer. Valemetostat tosylate is in a class of medications called EZH1/EZH2 inhibitors. It blocks proteins called EZH1 and EZH2, which may help slow or stop the spread of tumor cells. 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. Cabazitaxel injection is in a class of medications called microtubule inhibitors. It works by slowing or stopping the growth of tumor cells. Abiraterone acetate blocks tissues from making androgens (male hormones), such as testosterone. This may cause the death of tumor cells that need androgens to grow. It is a type of anti-androgen. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Lutetium Lu 177 vipivotide tetraxetan is in a class of medications called radiopharmaceuticals. It works by targeting and delivering radiation directly to tumor cells which damages and kills these cells. Assigning patients to targeted treatment based on genetic testing may help shrink or slow the cancer from growing
Detailed Description
The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. Evaluate objective response rate in patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for measurable disease, in each treatment arm. SECONDARY OBJECITVES: I. To determine safety and tolerability as determined by Common Terminology Criteria in Adverse Events (CTCAE) version 5.0 in each treatment arm. II. To evaluate 9-month radiographic progression free survival in each arm as defined by Prostate Cancer Clinical Trials Working Group 3 (PCWG-3) for patients with bone metastases and RECIST version 1.1 for patients with measurable disease. III. To evaluate radiographic progression free survival in each arm as defined by PCWG-3 for patients with bone metastases and RECIST version 1.1 for patients with measurable disease. IV. To evaluate prostate-specific antigen (PSA) response defined as ≥ 50% decline in PSA from baseline using PCWG-3 criteria in patients in each treatment arm. V. To evaluate time to PSA progression as defined by PCWG-3 criteria in patients in each treatment arm. VI. To evaluate time to occurrence of first symptomatic skeletal event. VII. To evaluate time to first subsequent anti-cancer therapy (including androgen receptor signaling agents, cytotoxic chemotherapy, immunotherapy, or investigational agents) or death. VIII. To evaluate overall survival, defined as time from registration to death due to any cause censored at the date of last follow-up, in each treatment arm. IX. To evaluate patient-reported outcomes (PRO) via Patient-Reported Outcomes (PRO)-CTCAE in each treatment arm. X. To evaluate duration of response as defined by RECIST version 1.1 for patients with measurable disease. CORRELATIVE OBJECTIVES: I. Correlate presence of molecular abnormalities with baseline clinical characteristics. II. Evaluate co-occurring molecular alterations within each biomarker arm. III. Evaluate mechanisms of response and resistance using available tissue (archival or baseline) and circulating cell free tumor DNA (cfDNA) and circulating tumor cells (CTCs) at baseline, on treatment, and at progression. IV. Evaluate efficacy parameters (objective response rate \[ORR\], PSA response, 9-month radiographic progression-free survival \[rPFS\], rPFS) based on arm allocation by: IVa. DNA versus RNA qualifying molecular alterations; IVb. Blood versus tissue-based qualifying molecular alteration; IVc. Primary versus metastasis qualifying molecular alteration. V. Evaluate efficacy parameters (ORR, PSA response, 9-month rPFS, rPFS) based on the following clinical parameters: Va. Presence or absence of visceral metastases at baseline; Vb. Number of prior lines of therapy for metastatic castration resistant cancer (mCRPC) (one versus \> 1); Vc. In patients having had prior exposure to taxane chemotherapy; Vd. Presence or absence of neuroendocrine differentiation at baseline. VI. Evaluate exceptional responders (defined as those with rPFS ≥ 18 months) and exceptional non-responders. VII. To determine how circulating biomarker quantification correlates with clinical features and outcomes. VIII. To determine the clinical impact of lineage plasticity alterations in predicting outcomes and response to therapy. EXPLORATORY OBJECTIVE: I. To compare patient-assessed adverse events via PRO-CTCAE™ with clinician-assessed adverse events in each treatment arm. OUTLINE: Patients undergo genetic testing on previously-collected tissue samples. Patients are then assigned to 1 of 3 arms based on genetic testing results and Molecular Tumor Board (MTB) decision. ARM A: Patients receive valemetostat tosylate orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive carboplatin intravenously (IV) over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive one of the following treatment regimens per treating physician: 1) Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2) Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. All patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) and bone scan throughout the trial. Patients may also undergo optional fludeoxyglucose F-18 (FDG) or prostate-specific membrane antigen (PSMA) positron emission tomography (PET), as well as optional blood collection throughout the trial. After completion of study treatment, patients without disease progression are followed every 2 months for the first 6 months and then every 3 months after that for up to 5 years. Patients with disease progression are followed every 6 months for 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRE-REGISTRATION: Histological or cytological evidence of prostate cancer. Patients with variant histologies including neuroendocrine, small cell and sarcomatoid prostate cancer are allowed to enroll and these will not be used as selection criteria for individual arms. Central pathology review is not required.
- •PRE-REGISTRATION: Measurable disease and/or non-measurable metastatic disease per RECIST version 1.
- •PRE-REGISTRATION: Tissue procured within 12 months of pre-registration (metastatic disease preferred over primary tissue, though both are acceptable) available for submission per Section 6.
- •For patients who have progressed on A032102 and are pre-registering again, repeat tissue procurement will not be mandated.
- •PRE-REGISTRATION: Molecular report available performed as part of standard of care testing via any Clinical Laboratory Improvement Act (CLIA)-certified next generation sequencing (NGS) assay. Patients may be assigned based on pre-determined qualifying molecular/DNA alterations as stated in Section 4.8 after receipt of local molecular testing by the A032102 molecular tumor board (MTB). Final determination of arm assignment will be determined by the MTB. For qualifying DNA alteration determined by the MTB, testing may be from tumor tissue collected at any time or circulating tumor DNA (ctDNA) within 12 months of pre-registration. If no qualifying DNA alteration is identified based on the CLIA-certified next generation sequencing assay and MTB review, Caris testing, should be performed for both DNA/RNA profiling. Arm assignment based RNA requires testing of tumor tissue collected within 12 months of pre-registration and MTB review.
- •PRE-REGISTRATION: Age ≥ 18 years.
- •REGISTRATION: Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND one or more of the following criteria (choose all the apply):
- •PSA progression, defined by at least 2 consecutive rising PSA values at a minimum of 1-week intervals with the most recent PSA value being 2.0 ng/mL or higher, if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal of anti-androgen therapy.
- •Radiographic progression per RECIST 1.1 criteria for soft tissue lesions
- •Bone metastasis progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
Exclusion Criteria
- Not provided
Arms & Interventions
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: PSMA PET Scan
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Computed Tomography
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Bone scan
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: FDG-Positron Emission Tomography
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: PSMA PET Scan
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Biospecimen Collection
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Genetic testing
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Computed Tomography
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Bone scan
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: FDG-Positron Emission Tomography
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Genetic testing
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Computed Tomography
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Biospecimen Collection
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Cabazitaxel
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Abiraterone Acetate
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Enzalutamide
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Genetic testing
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm A (genetic testing, valemetostat tosylate)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Valemetostat Tosylate
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: PSMA PET Scan
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Biospecimen Collection
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Bone scan
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: FDG-Positron Emission Tomography
Arm C (genetic testing, physician choice treatment)
Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Lutetium Lu 177 Vipivotide Tetraxetan
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Cabazitaxel
Arm B (genetic testing, carboplatin, cabazitaxel)
Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.
Intervention: Carboplatin
Outcomes
Primary Outcomes
Objective Response
Time Frame: Within 6 months from the start of treatment
Objective response is defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group 3 (PCWG3) for patients with measurable disease.
Secondary Outcomes
- Radiographic Progression Free Survival (rPFS)(From initiation of treatment up to 9 months)
- Overall Survival(Up to 5 years after study registration)
- Duration of Response(Up to 5 years after study registration)
- Prostate-specific antigen response(Through treatment completion, an average of one year)
- Time to systematic skeletal events(Up to 5 years after registration)
- Time to subsequent anti-cancer therapy(Up to 5 years after registration)
- Rate of Grade 3+ AEs(Up to 6 months after completion of study treatment)