Prostate Cancer
Conditions
Brief summary
This is a phase II clinical trial in patients with metastatic castration sensitive prostate cancer. The objective of the study is to determine the efficacy and further define the safety of the treatment combination. This study will evaluate dose levels of carboplatin AUC 4 with cabazitaxel 20 mg/m2. Patients will be treated with the combination of ADT and carboplatin and cabazitaxel for 6 cycles. After 6 cycles of chemotherapy, they will start abiraterone with ADT. The primary objective is to determine the percent of subjects that have no PSA or radiographic progression at 1 year. Secondary objectives will include determining the progression-free survival, time to PSA nadir and time to PSA progression of carboplatin and cabazitaxel in combination with ADT.
Interventions
DRUGCabazitaxel
20 mg/m2 Q 21 days
DRUGCarboplatin
AUC 4 Q21 Days x 6 cycles with ADT
DRUGAbiraterone
1000 mg PO daily
DRUGPrednisone
5 mg PO daily on chemotherapy completion
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. * Histologically confirmed prostate cancer. * High volume metastatic disease (defined as the presence of visceral metastases or ≥3 bone lesions). * ADT for ≤3 months by day 1 of study chemotherapy; Prior episodes of ADT are allowed (i.e. ADT used previously in courses of radiation). * Testosterone \<50 ng/dL. Patients must continue primary ADT with an LHRH analogue if they have not undergone orchiectomy. * ECOG Performance Status 0 or 1 (see Appendix A) * Patient has adequate bone marrow and organ function as defined by the following laboratory values: * Absolute neutrophil count ≥ 1.5 × 10\^9/L * Platelets ≥ 100 × 10\^9/L * Hemoglobin ≥ 9 g/dl * Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min * In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 x ULN. If the patient has liver metastases, ALT and AST \<5 x ULN * Total bilirubin \< ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome. * Sexually active males must use a condom during intercourse while taking study drugs and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Fertile males must use a condom with spermicide (double barrier method). * Age ≥ 18 years
Exclusion criteria
* Prior exposure to any chemotherapy, PARPi, or immunotherapy for prostate cancer. * Prior abiraterone or enzalutamide, unless therapy was for \< 2 weeks * Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose. * Other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is shorter, prior to day 1 of chemotherapy (with the exception of anti-androgens like bicalutamide). * PSA \<2.0 ng/mL at diagnosis. * If present, peripheral neuropathy must be ≤ Grade 1 * Patients with an active second malignancy that could, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. * Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria: * At least 4 weeks from prior therapy completion (including radiation and/or surgery) prior to starting the study treatment * Clinically stable CNS tumor at the time of screening. * Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement * Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of treating investigator. * Patient has a history of non-compliance to medical regimen or inability to grant consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-Specific Antigen (PSA) or Radiographic Progression | 1 Year | Number of patients who have no PSA or radiographic progression as determined by RECIST 1.1 or PCWG3 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 1 Year | Percentage of participants achieving Progression Free Survival |
| PSA Nadir | 1 Year | Time to PSA nadir |
| Incidence of Adverse Events | 1 Year | Safety and Tolerability |
| PSA Complete Response Rate | 1 Year | PSA complete response rate (PSA \<=0.2 ng/mL) in patient with mutations in DNA repair genes |
| PSA Progression | 1 Year | Time to PSA progression |
| Incidence of Homologous Recombination Deficiency (HRD) | 1 year | Incidence of HRD |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREmmanuel Antonarakis, MD
Masonic Cancer Center, University of Minnesota
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 30 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 61 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 61 |
| other Total, other adverse events | 60 / 61 |
| serious Total, serious adverse events | 8 / 61 |
Outcome results
None listed