Cabazitaxel and Prednisone in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well cabazitaxel and prednisone work in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as cabazitaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description
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PRIMARY OBJECTIVES: I. To test whether men with a poor initial response to androgen deprivation therapy (ADT) have a better front line therapeutic response to cabazitaxel as compared to historical controls of frontline metastatic castrate resistant prostate cancer (CRPC) therapy with abiraterone or enzalutamide. SECONDARY OBJECTIVES: I. To determine the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 response rate, progression free survival (PFS) by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria, and overall survival (OS). II. To evaluate safety and toxicity profile of cabazitaxel in patients with CRPC. TERTIARY OBJECTIVES: I. To collect serum and tumor tissue samples for molecular markers or signature predictive of cabazitaxel benefit (to include status of androgen receptor [AR] pathway, androgen biosynthetic pathway genes, adenosine triphosphate [ATP]-binding cassette sub-family B member 1 [ABCBI], multidrug resistance-associated protein 1 [MRP1], and other mediators of taxane resistance). OUTLINE: Patients receive cabazitaxel intravenously (IV) over 1 hour on day 1 and prednisone orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.

Official Title
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A Selective Frontline Cabazitaxel Therapeutic Pathway for Castration-Resistant Prostate Cancer With Integrated Biomarkers

Conditions
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Hormone-Resistant Prostate Cancer, Stage IV Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Cabazitaxel
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed prostate adenocarcinoma Metastatic disease Able and willing to provide informed consent and to comply with the study procedures Castration resistant disease defined as evidence of radiological and/or prostate specific antigen (PSA) progression despite castrate levels of testosterone (serum testosterone < 50 ng/dL [1.7 nmol/L]); for PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals; the first PSA value must be >= 4 (Prostate Cancer Working Group 2 [PCWG2] criteria) Eastern Cooperative Oncology Group (ECOG) performance status 0-2 At least 21 days have passed since completing radiotherapy (exception for radiotherapy: at least 7 days since completing a single fraction of =< 800 cGy to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of registration At least 21 days have passed since receiving any investigational agent at the time of registration At least 21 days have passed since major surgery Neuropathy =< grade 1 at the time of registration Has recovered from all therapy-related toxicity to =< grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) at the time of registration Poor prognosis disease as defined by any of the following: PSA nadir >=4.0, or Gleason score 8-10, or Time from ADT initiation to CRPC of =< 16 months Hemoglobin >= 90 g/L Neutrophils >= 1.5 x 10^9 /L Platelets >= 100 x 10^9/L Aspartate aminotransferase (AST) < 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) < 1.5 x ULN Bilirubin =< 1.0 x ULN (exceptions for Gilbert's syndrome) Creatinine =< 1.5 x ULN Exclusion Criteria: Prior therapy with cabazitaxel or to other drugs formulated with polysorbate 80 Prior taxanes for CRPC Prior enzalutamide, abiraterone or ketoconazole Other condition, illness, psychiatric condition, or laboratory abnormality that may increase the risk associated with administration of cabazitaxel, study participation, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study Histologic evidence of small cell/neuroendocrine prostate cancer Patients with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and up to 6 months after the last administered dose; the definition of effective method of contraception will be based on the investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (cabazitaxel, prednisone)<br>Patients receive cabazitaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: Cabazitaxel<br>* Given IV<br>* Other names: XRP-6258;Drug: Prednisone<br>* Given PO<br>* Other names: SK-Prednisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Response Rate, Defined as >= 50% Decline in PSA From Baseline Maintained for at Least 3 Weeks and Measured by the Same Laboratory, and Without Evidence of Other Disease Progression Documented at Time of Confirmatory Values | The response rate will be compared to a historical response rate of 20% using the exact binomial test for a single proportion. Confidence intervals for the response rate will be calculated using Wilson's method. | Up to 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events, Serious Adverse Events, and Discontinuations, Described and Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 | Incidence of adverse events, serious adverse events, and discontinuations, described and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 | Up to 28 days after discontinuation of study drug | 
| Overall Survival (OS) Defined as the Time Interval From the Date of Enrollment to the Date of Death Due to Any Cause. | Confidence intervals for the response rate will be calculated using Wilson's method. Medians will be estimated using the method of Kaplan and Meier, with confidence intervals estimated using Greenwood's method. | Up to 18 months. | 
| Progression-free Survival (PFS) Defined as the Time Interval Between the Date of Enrollment and the Date of the First Documentation by the Prostate Cancer Working Group 2 (PCWG2) Criteria. | Confidence intervals for the response rate will be calculated using Wilson's method. Medians will be estimated using the method of Kaplan and Meier, with confidence intervals estimated using Greenwood's method. | Approximately 5 months. | 
| Response Evaluation Criteria in Solid Tumors (RECIST) Response Defined as Radiographic Disease Progression | Confidence intervals for the response rate will be calculated using Wilson's method. Medians will be estimated using the method of Kaplan and Meier, with confidence intervals estimated using Greenwood's method. | Approximately 5 months. |