Hormone-Resistant Prostate Cancer, Stage IV Prostate Adenocarcinoma
Conditions
Brief summary
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
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.
Interventions
DRUGCabazitaxel
Given IV
DRUGPrednisone
Given PO
Sponsors
Sanofi
University of California, Davis
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 18 months. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| Overall Survival (OS) Defined as the Time Interval From the Date of Enrollment to the Date of Death Due to Any Cause. | Up to 18 months. | 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. |
| 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. | Approximately 5 months. | 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. |
| Response Evaluation Criteria in Solid Tumors (RECIST) Response Defined as Radiographic Disease Progression | Approximately 5 months. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Cabazitaxel, Prednisone) 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.
Cabazitaxel: Given IV
Prednisone: Given PO | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Treatment (Cabazitaxel, Prednisone) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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.
Time frame: Up to 18 months.
Population: The study was stopped due to poor accrual, and only 2 patients received study treatment. PSA was collected, but the number of evaluable patients was insufficient to perform analysis of this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Cabazitaxel, Prednisone) | 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 | 0 Participants |
Secondary
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
Time frame: Up to 28 days after discontinuation of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Cabazitaxel, Prednisone) | 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 | Neutrophil count decreased | 2 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Back pain | 1 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Diarrhea | 1 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Fatigue | 2 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Hot flashes | 1 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Non-cardiac chest pain | 1 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Pain | 1 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | Renal and urinary disorders - Other, specify | 1 participants |
| Treatment (Cabazitaxel, Prednisone) | 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 | White blood cell decreased | 2 participants |
Secondary
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.
Time frame: Up to 18 months.
Population: Study was terminated prematurely and data was not collected to assess this outcome measure.
Secondary
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.
Time frame: Approximately 5 months.
Population: Study was terminated prematurely and insufficient data was collected to assess this outcome measure.
Secondary
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.
Time frame: Approximately 5 months.
Population: Study was terminated prematurely and insufficient data was collected to assess this outcome measure.