UAMS - Translational Research Institute

Eligibility

Eligible Ages

Over 18 Years

Eligible Genders

Male

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- STEP 1 SCREENING REGISTRATION: NOTE: All participants must have biopsy tissue
submitted to MD Anderson Cancer Center prior to randomization for alteration
assessment. Participants must have determination of their AVPC-Molecular Pathologic
Signature immunohistochemistry (MSIHC) status from central assessment by the MD
Anderson Clinical Pathology Laboratory using Clinical Laboratory Improvement Act
(CLIA) certified immunohistochemistry (IHC) assays for TP53, RB1 and PTEN. In
addition, while not mandated, CLIA certified next generation sequencing (NGS) of
tumor deoxyribonucleic acid (DNA) and/or circulating tumor derived DNA (ctDNA)
assessment of AVPC-MS marker status will be collected from participants for whom it
is available

- STEP 1 SCREENING REGISTRATION: Participants must have a histologically confirmed
diagnosis of prostate cancer at the time of step 1 registration

- STEP 1 SCREENING REGISTRATION: Participants must have castrate-resistant prostate
cancer and metastatic disease by bone scan and/or CT/MRI (i.e., soft tissue,
visceral, lymph node)

- STEP 1 SCREENING REGISTRATION: Participants may have received any prior therapy, but
one must be docetaxel or contain docetaxel in either the castrate-sensitive and/or
castrate resistant disease state

- STEP 1 SCREENING REGISTRATION: Participants must be ≥ 18 years of age at the time of
step 1 screening registration

- STEP 1 SCREENING REGISTRATION: Participants must have solid tumor biopsy material
(formalin-fixed paraffin-embedded (FFPE) tissue blocks and/or 10 cut slides on
four-micron thick unstained positive charged slides of FFPE tissue) available for
submission for alterations in TP53, RB1 and PTEN by IHC using CLIA certified assays
in the MD Anderson Clinical Pathology Laboratory. This specimen is required for
central assessment of the AVPC-MSIHC regardless of whether the site has already
locally evaluated the AVPC-MS status

- STEP 1 SCREENING REGISTRATION: Tumor samples submitted for analysis must have been
collected within 12 months prior to step 1 screening registration. Samples from
metastatic lesions collected in the castrate-resistant disease state are preferable
but not mandatory. Samples obtained during the hormone-naive disease state are
acceptable if collected within 12 months of step 1 screening registration. If more
than one tumor sample exists, the sample obtained closest to the date of
registration should be submitted to MDACC for analysis

- NOTE: Sites will receive an email from Southwest Oncology Group (SWOG)
Statistics and Data Management Center containing participant results of
Aggressive Variant Prostate Cancer Molecular Signature (AVPC-MS) assessment
within 5-12 business days after tissue submission to MD Anderson Clinical
Pathology Laboratory. The participant's AVPC-MS signature result (positive or
negative) is required BEFORE randomization on to step 2. If sites receive a
non-evaluable AVPC-MS signature result, SWOG Statistics and Data Management
Center will provide instructions for resubmission

- STEP 1 SCREENING REGISTRATION: NOTE: As a part of the Oncology Patient Enrollment
Network (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

- STEP 1 SCREENING REGISTRATION: 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. Documentation of informed consent via remote
consent is allowed

- 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

- STEP 2 RANDOMIZATION: NOTE: Participants must be registered to step 2 randomization
within 70 days after registration to step 1. Participants must plan to start
protocol therapy no more than 14 days after step 2 randomization

- STEP 2 RANDOMIZATION: Participants must have castrate levels of testosterone with a
baseline level < 50ng/dL within 28 days prior to step 2 randomization

- STEP 2 RANDOMIZATION: Participants must have evidence for metastatic prostate cancer
by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). Visceral
and/or soft-tissue metastases must be ≥ 1.0 cm in diameter and lymph nodes must be >
1.5 cm diameter in the short axis. Scans must be obtained within 28 days prior to
randomization

- NOTE: All disease must be assessed and documented on the
baseline/pre-registration tumor assessment form

- STEP 2 RANDOMZIATION: Participants must have progressive disease (PD) in the opinion
of the treating investigator according to any of the following criteria

- Progression in measurable disease (RECIST 1.1 criteria). Patient with
measurable disease must have at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded). Each
lesion must be at least 10 mm when measured by computed tomography (CT) [CT
scan thickness no greater than 5 mm] or magnetic resonance imaging (MRI). Lymph
nodes should be ≥ 15 mm in short axis. Previously irradiated lesions, primary
prostate lesion and bone lesions will be considered non-measurable disease

- Progression in bone as evidenced by:

- Appearance of 2 or more new bone lesions on bone scan (BS). If equivocal,
they must be confirmed by other imaging modalities (CT; MRI), and/or
repeat BS > 4 weeks later

- Appearance of a new lytic lesion(s) and/or increasing size of an existing
lesion by CT/MRI, since AVPC tumors may produce lytic bone lesions that
are not detected on conventional bone scans

- Rising prostate-specific antigen (PSA) defined (Prostate Cancer Working Group 2
[PCWG2]) as at least two consecutive rises in PSA to be documented over a
reference value (measure 1) taken at least one week apart. The first rising PSA
(measure 2) should be taken at least 7 days after the reference value. A third
confirmatory PSA measure is required (2nd beyond the reference level) to be
greater than the second measure and it must be obtained at least 7 days after
the 2nd measure. If this is not the case, a fourth PSA measure is required to
be taken and be greater than the 2nd measure. In case of progression based on
rising PSA only, the first rising PSA (measure 2) must be obtained within 6
months of initiation of androgen receptor (AR) targeted therapy (≤ 6 months)

- Clinical progression. Increasing symptoms unequivocally attributed to disease
progression as judged by the treating physician

- STEP 2 RANDOMIZATION: Participants must not have received prior cabazitaxel or
carboplatin

- STEP 2 RANDOMIZATION: Participants must not be receiving treatment on another
therapeutic clinical trial at the time of randomization. Chemotherapies, bone
targeting therapies, immunotherapies and clinical trial agents must be discontinued
≥ 21 days prior to randomization. Stereotactic radiation (SART) must be discontinued
≥ 3 days prior to randomization

- STEP 2 RANDOMIZATION: Participants must not be receiving radiation therapy or
kyphoplasty-vertebroplasty within 14 days prior to randomization or major surgery
(e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days
prior to step 2 randomization

- STEP 2 RANDOMIZATION: Participants must not have untreated fractures and/or cord
compression

- STEP 2 RANDOMIZATION: Participants must not have symptomatic uncontrolled brain
metastases. Properly treated brain metastases (i.e., with stereotactic radiation)
within 14 days are allowed

- STEP 2 RANDOMIZATION: Participants must have Zubrod performance status of 0 - 2
within 28 days prior to step 2 randomization

- STEP 2 RANDOMIZATION: Participants must have a complete medical history and physical
exam within 28 days prior to step 2 randomization

- STEP 2 RANDOMIZATION: Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days
prior to step 2 randomization)

- STEP 2 RANDOMIZATION: Platelets ≥ 100 x 10^3/uL (unless clinical evidence of bone
marrow infiltration by tumor in which case > 75 x 10^3/uL are allowed) (within 28
days prior to step 2 randomization)

- STEP 2 RANDOMIZATION: Total bilirubin ≤ institutional upper limit of normal (ULN)
with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome or if
the participant has liver metastases and/or acute tumor associated illness < 4x ULN
(within 28 days prior to step 2 randomization)

- STEP 2 RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase
(ALT) ≤ 3 × institutional ULN (or if participant has liver metastases and/or acute
tumor-associated illness, ≤ 4x institutional ULN) (within 28 days prior to step 2
randomization)

- STEP 2 REGISTRATION: Participants must have a calculated creatinine clearance ≥ 30
mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and
processed within 28 days prior to step 2 randomization

- STEP 2 RANDOMIZATION: Participants with peripheral neuropathy must have ≤ grade 2
peripheral neuropathy (Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0) (within 28 days prior to step 2 randomization)

- STEP 2 RANDOMIZATION: 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

- STEP 2 RANDOMIZATION: Participants 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 the treatment
regimen

- STEP 2 RANDOMIZATION: Participants with known human immunodeficiency virus
(HIV)-infection must be on effective anti-retroviral therapy at registration and
have undetectable viral load test on the most recent test results obtained within 6
months prior to registration

- STEP 2 RANDOMIZATION: Participants must be offered the opportunity to participate in
specimen banking. With participant consent, specimens must be collected and
submitted via the SWOG Specimen Tracking System