Rapid Cycle Combination Therapy in Treating Patients with Metastatic Castrate-Resistant Prostate Cancer
Inclusion Criteria
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Metastatic castrate resistant prostate cancer, defined by progressive disease based on either rising PSA, new bone metastases, or progression of measurable disease on imaging, according to Prostate Cancer Working Group 2 (PCWG2) guidelines, despite androgen deprivation therapy
- Ongoing androgen deprivation therapy with a GnRH analogue, GnRH antagonist, or bilateral orchiectomy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Serum testosterone level < 50 ng/dL
- Absolute neutrophil count > 1,500/uL
- Platelet count > 100,000/uL
- Hemoglobin > 9 g/dL
- Creatinine < 2 mg/dL
- Total bilirubin < 1.5 times the upper limit of normal
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 1.5 times the upper limit of normal
Exclusion Criteria
- History of uncontrolled seizure disorder
- Clinically significant cardiovascular disease including: * Myocardial infarction or uncontrolled angina within 6 months * Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past * Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
- Have used or plan to use from 30 days prior to enrollment through the end of the study medication known to lower the seizure threshold or prolong the QT interval
- Major surgery within 4 weeks of enrollment
- Radiation therapy within 4 weeks of enrollment
- Prior use of abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, carboplatin, or radium-223 for the treatment of castration-resistant disease * Prior docetaxel use in the hormone-sensitive disease setting is allowed, but must be completed >= 4 weeks prior to enrollment * Prior sipuleucel-T use is allowed, but must be completed >= 4 weeks prior to enrollment * Concurrent use of zolendronic acid or denosumab is allowed on study
New York
New York
PRIMARY OBJECTIVE:
I. To evaluate time to disease progression, as determined by either prostate specific antigen (PSA) or radiographic progression, after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with metastatic castration-resistant prostate cancer (mCRPC).
SECONDARY OBJECTIVES:
I. To evaluate overall survival.
II. To assess PSA response rate with each treatment module.
III. To assess changes to alkaline phosphatase levels.
IV. To assess safety of the rapidly-cycling, non-cross reactive regimen.
EXPLORATORY OBJECTIVES:
I. To evaluate the correlation of a peripheral whole-blood ribonucleic acid (RNA) signature with clinical outcome measures during and after treatment.
II. To evaluate changes to AR-V7 expression in circulating tumor cells (CTCs) with different treatment modalities and clinical outcomes.
OUTLINE:
MODULE I: Patients receive abiraterone acetate orally (PO) once daily (QD). Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
MODULE II: Patients receive cabazitaxel IV on day 1 and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
MODULE III: Patients receive enzalutamide PO QD. Patients with known bone metastases also receive radium Ra 223 dichloride IV on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 weeks for 1 year.
Trial Phase Phase II
Trial Type Treatment
Lead Organization
Icahn School of Medicine at Mount Sinai
Principal Investigator
Bobby Liaw
- Primary ID 16-1593
- Secondary IDs NCI-2017-00934
- Clinicaltrials.gov ID NCT02903160