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

• Sponsor: University of California, Davis (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02844582
• Collaborator: Sanofi (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 17.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hormone-Resistant Prostate Cancer; Stage IV Prostate Adenocarcinoma	Drug: Cabazitaxel; Drug: Prednisone	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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).

2. To evaluate safety and toxicity profile of cabazitaxel in patients with CRPC.

TERTIARY OBJECTIVES:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Selective Frontline Cabazitaxel Therapeutic Pathway for Castration-Resistant Prostate Cancer With Integrated Biomarkers
• Actual Study Start Date: Dec 20, 2017
• Actual Primary Completion Date: Jun 4, 2019
• Actual Study Completion Date: Jun 4, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: Cabazitaxel; Given IV; Other Names: Jevtana RPR-116258A Taxoid XRP6258 XRP-6258 ; Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis
• Sanofi

Investigators

• Principal Investigator: Christopher Evans, University of California, Davis

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 23, 2018
• Informed Consent Form - Sep 10, 2018

More Information

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT02844582
• Other Study ID Numbers: 868922; UCDCC#261; UCDCC#261; NCI-2016-00961
• First Posted: Jul 26, 2016
• Last Update Posted: Jan 25, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Cortisone

Study Results

Participant Flow

Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 50%
>=65 years	1 50%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	2 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Measure Participants	2
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	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
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
Time Frame	Up to 28 days after discontinuation of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Measure Participants	2
Back pain	1 50%
Diarrhea	1 50%
Fatigue	2 100%
Hot flashes	1 50%
Neutrophil count decreased	2 100%
Non-cardiac chest pain	1 50%
Pain	1 50%
Renal and urinary disorders - Other, specify	1 50%
White blood cell decreased	2 100%

3. Secondary Outcome

Title	Overall Survival (OS) Defined as the Time Interval From the Date of Enrollment to the Date of Death Due to Any Cause.
Description	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.

Outcome Measure Data

Analysis Population Description

Study was terminated prematurely and data was not collected to assess this outcome measure.

Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Measure Participants	0

4. Secondary Outcome

Title	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.
Description	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.

Outcome Measure Data

Analysis Population Description

Study was terminated prematurely and insufficient data was collected to assess this outcome measure.

Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Measure Participants	0

5. Secondary Outcome

Title	Response Evaluation Criteria in Solid Tumors (RECIST) Response Defined as Radiographic Disease Progression
Description	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.

Outcome Measure Data

Analysis Population Description

Study was terminated prematurely and insufficient data was collected to assess this outcome measure.

Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
Measure Participants	0

Adverse Events

Time Frame	Up to 28 days after discontinuation of study drug.
Adverse Event Reporting Description	Number of Participants with Adverse Events.
Arm/Group Title	Treatment (Cabazitaxel, Prednisone)
Arm/Group Description	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
All Cause Mortality
	Treatment (Cabazitaxel, Prednisone)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Treatment (Cabazitaxel, Prednisone)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Cabazitaxel, Prednisone)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Diarrhea	1/2 (50%)
General disorders
Fatigue	2/2 (100%)
Non-cardiac chest pain	1/2 (50%)
Pain	1/2 (50%)
Investigations
Neutrophil count decreased	2/2 (100%)
White blood cell decreased	2/2 (100%)
Musculoskeletal and connective tissue disorders
Back pain	1/2 (50%)
Nervous system disorders
Headache	1/2 (50%)
Renal and urinary disorders
Renal and urinary disorders - Other, specify	1/2 (50%)
Vascular disorders
Hot flashes	1/2 (50%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.