Carboplatin, Cabazitaxel and Abiraterone in Treating Patients with Metastatic Castration Sensitive Prostate Cancer
- Willing and able to provide, or have a legally authorized representative provide, written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. * NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
- Histologically confirmed prostate cancer.
- High volume metastatic disease defined as the presence of visceral metastases or >= 3 bone lesions on standard computed tomography (CT) or bone scan imaging. Patients with high volume disease on novel imaging scans including Axumin positron emission tomography (PET) or prostate-specific membrane antigen (PSMA) PET are only eligible if they meet criteria on standard CT and bone scan
- 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 for patients who have initiated ADT > 1 month prior to study treatment start. Patients must continue primary ADT with an luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy. Patients who have not yet started ADT at the time of enrollment may initiate ADT via LHRH agonist or antagonist therapy during the screening period and will not be required to document a castrate level of testosterone prior to initiating chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Absolute neutrophil count >= 1.5 x 10^9/L.
- Platelets >= 100 x 10^9/L.
- Hemoglobin >= 9 g/dl.
- Serum creatinine =< 1.5 mg/dL or estimated creatinine clearance >= 50 ml/min.
- In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (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).
- Prior exposure to any chemotherapy, PARP inhibitor (PARPi), or immunotherapy for prostate cancer.
- Pure small cell carcinoma
- Prior abiraterone, apalutamide, darolutamide, or enzalutamide, unless therapy was for < 4 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.
- Known history of severe hypersensitivity to drugs formulated with polysorbate 80
- 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.
I. To determine the proportion of patients who have no prostate-specific antigen (PSA) or radiographic progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Prostate Cancer Working Group (PCWG)3 criteria at 1 year with 6 cycles of carboplatin and cabazitaxel followed by continued abiraterone.
I. To determine the progression‐free survival, time to PSA nadir and time to PSA progression in men with high volume metastatic castration sensitive prostate cancer treated with cabazitaxel and carboplatin in combination with androgen deprivation therapy (ADT).
II. To determine the safety and tolerability of combination treatment of cabazitaxel and carboplatin in men with metastatic prostate cancer.
III. Incidence of homologous repair defects (HRD) in this population.
IV. To compare PSA complete response rate (PSA < 0.2 ng/ml) at 1 year in patients with and without mutations in deoxyribonucleic acid (DNA) repair genes as well as various molecular subtypes (luminal/basal).
I. To obtain circulating tumor cells (CTCs) to evaluate for reversion mutations, conformational changes, and validate HRD phenotype with Epic Sciences.
II. To analyze and track changes in cell-free deoxyribonucleic acid (cfDNA), particularly for the emergence of alterations that would confer resistance.
III. To apply the PAM50 gene expression signature (PAM50) classifier to subtype archival primary or metastatic prostate cancer samples into basal or luminal A versus (vs.) B subtypes to gauge response to carboplatin and cabazitaxel.
Patients receive cabazitaxel intravenously (IV) over 60 minutes on day 1, carboplatin IV over 60 minutes on day 1, and prednisone orally (PO) twice daily (BID). Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Within 30 days after the end of cycle 6, patients receive abiraterone acetate PO once daily (QD) and prednisone PO QD in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.
Trial Phase Phase II
Trial Type Treatment
University of Minnesota / Masonic Cancer Center
Charles James Ryan
- Primary ID 2018LS158
- Secondary IDs NCI-2019-03566
- Clinicaltrials.gov ID NCT03934840