NCT06632977

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

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
474

participants targeted

Target at P75+ for phase_2

Timeline
103mo left

Started Feb 2025

Longer than P75 for phase_2

Geographic Reach
1 country

94 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress13%
Feb 2025Oct 2034

First Submitted

Initial submission to the registry

October 1, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

October 9, 2024

Completed
4 months until next milestone

Study Start

First participant enrolled

February 6, 2025

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 11, 2030

Expected
4.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 11, 2034

Last Updated

March 4, 2026

Status Verified

March 1, 2026

Enrollment Period

5.2 years

First QC Date

October 1, 2024

Last Update Submit

March 2, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Objective Response

    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.

    Within 6 months from the start of treatment

Secondary Outcomes (7)

  • 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

  • +2 more secondary outcomes

Other Outcomes (1)

  • National Cancer Institute PRO-CTCAEâ„¢ data

    Up to 5 years after completion of study treatment

Study Arms (3)

Arm A (genetic testing, valemetostat tosylate)

EXPERIMENTAL

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.

Other: Genetic testingDrug: Valemetostat TosylateProcedure: Magnetic Resonance ImagingProcedure: Computed TomographyProcedure: Bone scanProcedure: FDG-Positron Emission TomographyProcedure: PSMA PET ScanProcedure: Biospecimen Collection

Arm B (genetic testing, carboplatin, cabazitaxel)

EXPERIMENTAL

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.

Other: Genetic testingProcedure: Magnetic Resonance ImagingProcedure: Computed TomographyProcedure: Bone scanProcedure: FDG-Positron Emission TomographyProcedure: PSMA PET ScanProcedure: Biospecimen CollectionDrug: CarboplatinDrug: Cabazitaxel

Arm C (genetic testing, physician choice treatment)

EXPERIMENTAL

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.

Other: Genetic testingProcedure: Magnetic Resonance ImagingProcedure: Computed TomographyProcedure: Bone scanProcedure: FDG-Positron Emission TomographyProcedure: PSMA PET ScanProcedure: Biospecimen CollectionDrug: CabazitaxelDrug: Abiraterone AcetateDrug: EnzalutamideDrug: Lutetium Lu 177 Vipivotide Tetraxetan

Interventions

PSMA PET ScanPROCEDURE

Undergo PSMA PET

Also known as: Prostate-specific Membrane Antigen PET
Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

undergo blood collection

Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

Given IV

Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

Given PO

Arm C (genetic testing, physician choice treatment)

Given PO

Also known as: Xtandi
Arm C (genetic testing, physician choice treatment)

Given IV

Also known as: Pluvicto
Arm C (genetic testing, physician choice treatment)

undergo genetic testing

Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

Given PO

Arm A (genetic testing, valemetostat tosylate)

undergo Magnetic Resonance Imaging

Also known as: MRI
Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

undergo Computed Tomography

Also known as: CAT Scan, CT Scan
Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)
Bone scanPROCEDURE

undergo Bone scan

Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

Undergo FDG PET

Arm A (genetic testing, valemetostat tosylate)Arm B (genetic testing, carboplatin, cabazitaxel)Arm C (genetic testing, physician choice treatment)

Given IV

Arm B (genetic testing, carboplatin, cabazitaxel)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 1.1.
  • 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 6.2. 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.
  • REGISTRATION: Patients selected to receive lutetium Lu 177 vipivotide tetraxetan treatment are required to have prostate-specific membrane antigen (PSMA) positive mCRPC as determined by investigator assessment. For reference, in the VISION trial this was defined as at least 1 PSMA+ metastatic lesion (defined as uptake greater than that of liver parenchyma in lesions of any size in any organ system) and no PSMA- lesions (defined as uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any solid organ lesion with a short axis of at least 1.0 cm, or in any bone lesion with a soft-tissue component of at least 1.0 cm in the short axis).
  • REGISTRATION: Prior treatment with androgen receptor signaling inhibitor (ARSI) in either the metastatic hormone sensitive setting or mCRPC is required. Prior taxane therapy in either metastatic hormone sensitive setting or mCRPC is mandated unless patient is taxane ineligible or the patient refuses taxane therapy. Prior lutetium LU177 vipivotide tetraxetan treatment is permitted but not mandated. Patients with known germline or somatic deleterious BRCA 1/2 mutations must have received a prior PARPi.
  • REGISTRATION: Resolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable grade 2 toxicities (defined as no worsening to \> grade 2 for at least 3 months prior to registration and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, comprised of:
  • Chemotherapy-induced neuropathy
  • Fatigue
  • Residual toxicities from prior treatment: Grade 1 or grade 2 endocrinopathies which may include: Hypothyroidism/hyperthyroidism. type I diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation (vitiligo)
  • +62 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (94)

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

RECRUITING

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

RECRUITING

UC San Diego Health System - Encinitas

Encinitas, California, 92024, United States

RECRUITING

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

RECRUITING

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, 80909, United States

RECRUITING

Memorial Hospital North

Colorado Springs, Colorado, 80920, United States

RECRUITING

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

RECRUITING

Cancer Care and Hematology-Fort Collins

Fort Collins, Colorado, 80528, United States

RECRUITING

UCHealth Greeley Hospital

Greeley, Colorado, 80631, United States

RECRUITING

Medical Center of the Rockies

Loveland, Colorado, 80538, United States

RECRUITING

Beebe South Coastal Health Campus

Millville, Delaware, 19967, United States

RECRUITING

Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

RECRUITING

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

RECRUITING

Beebe Health Campus

Rehoboth Beach, Delaware, 19971, United States

RECRUITING

Jupiter Medical Center

Jupiter, Florida, 33458, United States

RECRUITING

Tripler Army Medical Center

Honolulu, Hawaii, 96859, United States

RECRUITING

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, 83814, United States

SUSPENDED

Illinois CancerCare-Bloomington

Bloomington, Illinois, 61704, United States

RECRUITING

Illinois CancerCare-Canton

Canton, Illinois, 61520, United States

RECRUITING

Illinois CancerCare-Eureka

Eureka, Illinois, 61530, United States

RECRUITING

Cancer Care Center of O'Fallon

O'Fallon, Illinois, 62269, United States

RECRUITING

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, 61350, United States

RECRUITING

Illinois CancerCare-Pekin

Pekin, Illinois, 61554, United States

RECRUITING

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

RECRUITING

Illinois CancerCare-Peru

Peru, Illinois, 61354, United States

RECRUITING

Memorial Hospital East

Shiloh, Illinois, 62269, United States

RECRUITING

Illinois CancerCare - Washington

Washington, Illinois, 61571, United States

RECRUITING

McFarland Clinic - Ames

Ames, Iowa, 50010, United States

RECRUITING

University of Iowa Healthcare Cancer Services Quad Cities

Bettendorf, Iowa, 52722, United States

RECRUITING

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061, United States

RECRUITING

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States

RECRUITING

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606, United States

RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

Saint Elizabeth Healthcare Edgewood

Edgewood, Kentucky, 41017, United States

RECRUITING

Saint Elizabeth Healthcare Fort Thomas

Fort Thomas, Kentucky, 41075, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute at Foxborough

Foxborough, Massachusetts, 02035, United States

RECRUITING

Dana Farber-Merrimack Valley

Methuen, Massachusetts, 01844, United States

RECRUITING

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional

Milford, Massachusetts, 01757, United States

RECRUITING

Dana-Farber/Brigham and Women's Cancer Center at South Shore

South Weymouth, Massachusetts, 02190, United States

RECRUITING

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, 48188, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, 48118, United States

RECRUITING

University of Michigan Health - Sparrow Lansing

Lansing, Michigan, 48912, United States

RECRUITING

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197, United States

RECRUITING

Essentia Health Saint Joseph's Medical Center

Brainerd, Minnesota, 56401, United States

RECRUITING

Essentia Health Cancer Center

Duluth, Minnesota, 55805, United States

RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

RECRUITING

MU Health - University Hospital/Ellis Fischel Cancer Center

Columbia, Missouri, 65212, United States

ACTIVE NOT RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

RECRUITING

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Mount Sinai Hospital

New York, New York, 10029, United States

SUSPENDED

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Essentia Health Cancer Center-South University Clinic

Fargo, North Dakota, 58103, United States

RECRUITING

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Guthrie Medical Group PC-Robert Packer Hospital

Sayre, Pennsylvania, 18840, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

RECRUITING

UT Southwestern Simmons Cancer Center - RedBird

Dallas, Texas, 75237, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, 76104, United States

RECRUITING

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas, 75080, United States

RECRUITING

Bon Secours Memorial Regional Medical Center

Mechanicsville, Virginia, 23116, United States

RECRUITING

Bon Secours Saint Francis Medical Center

Midlothian, Virginia, 23114, United States

RECRUITING

Bon Secours Richmond Community Hospital

Richmond, Virginia, 23223, United States

RECRUITING

Bon Secours Saint Mary's Hospital

Richmond, Virginia, 23226, United States

RECRUITING

Bon Secours Cancer Institute at Reynolds Crossing

Richmond, Virginia, 23230, United States

RECRUITING

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

Swedish Cancer Institute-Edmonds

Edmonds, Washington, 98026, United States

RECRUITING

West Virginia University Charleston Division

Charleston, West Virginia, 25304, United States

ACTIVE NOT RECRUITING

Edwards Comprehensive Cancer Center

Huntington, West Virginia, 25701, United States

RECRUITING

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

RECRUITING

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin, 53051, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Drexel Town Square Health Center

Oak Creek, Wisconsin, 53154, United States

RECRUITING

Froedtert West Bend Hospital/Kraemer Cancer Center

West Bend, Wisconsin, 53095, United States

RECRUITING

Related Publications (1)

  • Chen YW, Xiu J, Poorman KA, Ryan CJ, Gilg B, Oberley MJ, Sura G, Sledge GW Jr, Zhao SG, Tan A, Beltran H, McKay RR. Clinical Utility of Transcriptomic Signatures to Identify Androgen Receptor and Neuroendocrine Signaling in Prostate Cancer. JCO Precis Oncol. 2026 Mar;10:e2500756. doi: 10.1200/PO-25-00756. Epub 2026 Mar 5.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Genetic TestingMagnetic Resonance SpectroscopyGlutamate Carboxypeptidase IICarboplatincabazitaxelAbiraterone AcetateenzalutamidePluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesGenetic TechniquesGenetic ServicesHealth ServicesHealth Care Facilities Workforce and ServicesDiagnostic ServicesPreventive Health ServicesSpectrum AnalysisChemistry Techniques, AnalyticalCarboxypeptidasesExopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesMetalloexopeptidasesMetalloproteasesCoordination ComplexesOrganic ChemicalsAndrostenesAndrostanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Rana McKay, MD

    Alliance for Clinical Trials in Oncology

    STUDY CHAIR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 1, 2024

First Posted

October 9, 2024

Study Start

February 6, 2025

Primary Completion (Estimated)

April 11, 2030

Study Completion (Estimated)

October 11, 2034

Last Updated

March 4, 2026

Record last verified: 2026-03

Locations