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Enzalutamide and Cabazitaxel in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02522715
Recruitment Status : Recruiting
First Posted : August 13, 2015
Last Update Posted : July 30, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Julie Graff, OHSU Knight Cancer Institute

Brief Summary:
This phase I/II trial studies the side effects and best dose of cabazitaxel when given together with enzalutamide in treating patients with prostate cancer that has spread to other places in the body (metastatic) and has not responded to treatment with hormones or no longer responds to treatment with hormones (hormone-resistant). Drugs used in chemotherapy, such as cabazitaxel, 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. Androgen can cause the growth of prostate cancer cells. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of androgen by the tumor cells. Giving cabazitaxel together with enzalutamide may work better in treating metastatic, hormone-resistant prostate cancer.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer AJCC v7 Drug: Cabazitaxel Drug: Enzalutamide Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Prednisone Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Concurrent Chemohormonal Therapy Using Enzalutamide (MDV-3100) and Cabazitaxel in Patients With Metastatic Castration Resistant Prostate Cancer
Actual Study Start Date : October 13, 2015
Estimated Primary Completion Date : January 31, 2019
Estimated Study Completion Date : August 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Treatment (cabazitaxel, enzalutamide)
Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of course 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Courses repeat every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.
Drug: Cabazitaxel
Given IV
Other Names:
  • Jevtana
  • RPR-116258A
  • Taxoid XRP6258
  • XRP-6258

Drug: Enzalutamide
Given PO
Other Names:
  • ASP9785
  • MDV3100
  • Xtandi

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

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




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (Phase I) [ Time Frame: Up to 42 days ]
    Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval using exact method.

  2. PSA response 1, defined as >= 90% PSA decline from baseline [ Time Frame: Baseline to week 28 ]
    Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval using exact method. As an exploratory subgroup analysis, the various PSA response rates will be estimated in two subgroups that either received prior abiraterone or had not received prior abiraterone.


Secondary Outcome Measures :
  1. Incidence of adverse events graded by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 [ Time Frame: Up to 28 days after the last dose of study medication ]
    Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval using exact method.

  2. Overall survival [ Time Frame: Up to 5 years ]
    Descriptive statistical analysis will be conducted. The median overall survival will be estimated with 95% confidence interval (if available). Kaplan-Meier plot will be used to graphically illustrate the overall survival distribution.

  3. Pharmacokinetic parameters of cabazitaxel: Max plasma concentration (Cmax) [ Time Frame: Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of courses 1 and 2 ]
    Mean plasma concentration (Cmax) will be plotted over time for cabazitaxel (day 1, cycle 1) and cabazitaxel co-administered with enzalutamide (day 1, cycle 2). Noncompartmental pharmacokinetic analysis will be performed on individual concentration-time data to calculate maximum concentration from 0 hours to last measurable concentration and to infinity, and half-life, for cabazitaxel administered alone or coadministered with enzalutamide.

  4. Pharmacokinetic parameters of cabazitaxel: Mean Area Under the Curve (AUC) [ Time Frame: Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of courses 1 and 2 ]
    Mean area under the curve (AUC) will be plotted over time for cabazitaxel (day 1, cycle 1) and cabazitaxel co-administered with enzalutamide (day1, cycle 2). Noncompartmental pharmacokinetic analysis will be performed on individual concentration-time data to calculate AUC from 0 hours to last measurable concentration for cabazitaxel administered alone or coadministered with enzalutamide.

  5. Pharmacokinetic parameters of cabazitaxel: Mean Cabazitaxel Half-Life [ Time Frame: Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of courses 1 and 2 ]
    Mean cabazitaxel half-life will be plotted over time for cabazitaxel (day 1, cycle 1) and cabazitaxel co-administered with enzalutamide (day1, cycle 2). Noncompartmental pharmacokinetic analysis will be performed on individual concentration-time data to calculate half-life from 0 hours to last measurable concentration for cabazitaxel administered alone or coadministered with enzalutamide.

  6. PSA response 2, defined as >= 50% PSA decline from baseline [ Time Frame: Baseline to week 28 ]
    Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval using exact method. As an exploratory subgroup analysis, the various PSA response rates will be estimated in two subgroups that either received prior abiraterone or had not received prior abiraterone.

  7. PSA response 3, defined as >= 30% PSA decline from baseline [ Time Frame: Baseline to week 28 ]
    Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval using exact method. As an exploratory subgroup analysis, the various PSA response rates will be estimated in two subgroups that either received prior abiraterone or had not received prior abiraterone.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metastatic CRPC
  • Willing to provide a tumor sample via biopsy from a metastatic site of disease to be collected at screening if safe and feasible per discretion of treating investigator; adequate archival metastatic tissue can be used, if available, in lieu of baseline biopsy if done when patient had CRPC; patients without a site amenable to biopsy and lack of archival tissue may still join the study
  • Evidence of prostate cancer progression by any of the following criteria: radiographic or PSA criteria, or symptomatic progression related to prostate cancer
  • Castrate testosterone levels (< 50 ng/dL) achieved by orchiectomy or maintenance on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
  • Histologic confirmation of original prostate cancer diagnosis per institutional standard; life expectancy of greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Leukocytes >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin within normal institutional limits (or < 2 X the upper limit of normal in those with Gilbert?s disease)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X institutional upper limit of normal
  • Creatinine within less than the institutional upper limit of normal
  • Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Subject agrees to use a double barrier method of birth control during the course of study treatment period with enzalutamide and/or cabazitaxel treatment and for at least 3 months after the study is discontinued

    • A double-barrier method of contraception involves the use of a condom in combination with 1 of the following: contraceptive sponge, diaphragm, or cervical ring with spermicidal gel or foam
    • Subject who has had a vasectomy at least 6 months prior to starting study treatment period and those whose female sexual partner(s) are more than 55 years of age and postmenopausal for at least 2 years or surgically sterile (tubal ligation, hysterectomy, or bilateral oophorectomy) agree to use at least a condom
  • Ability to understand, and the willingness to sign, a written informed consent document, as well as comply with study requirements
  • Must have appropriate wash out (> 6 half-lives) of androgen receptor antagonists, 5 alpha reductase inhibitors or ketoconazole prior to the start of cycle 1; if the agent is not in the table below, the washout should be 2 weeks

    • Bicalutamide; approximate half-life: 6 days; washout period required: 36 days
    • Flutamide; approximate half-life: 6 hours; washout period required: 36 hours
    • Nilutamide approximate half-life: 4 days; washout period required: 24 days
    • Finasteride; approximate half-life: 8 hours; washout period required: 48 hours
    • Aminoglutethimide; approximate half-life: 15 hours; washout period required: 4 days
    • Ketoconazole; approximate half-life: 8 hours; washout period required: 48 hours

Exclusion Criteria:

  • Prior chemotherapy for mCRPC prostate cancer; chemotherapy given neoadjuvantly, adjuvantly, or for hormone sensitive metastatic disease is permitted as long as the cancer did not progress on chemotherapy AND > 6 months have elapsed
  • Patients may not have received any other investigational agents within the last 14 days at the time of treatment start
  • Patients may not have received enzalutamide or ARN-509 (another androgen receptor antagonist) in the past
  • Patients may not have received cabazitaxel in the past
  • Subject has clinical signs suggestive of high or imminent risks for pathological fracture, spinal cord compression and/or cauda equina syndrome
  • History of severe hypersensitivity reaction (>= grade 3) to docetaxel, polysorbate 80 containing drugs, or any of the capsule components of enzalutamide, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene
  • Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 family 3, subfamily A, polypeptide 4/5 (3A4/5); (a one-week wash-out period is necessary for patients who are already on these treatments)
  • Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Subject has a history of seizure or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke in the past 6 months, primary brain tumors, brain metastases, prior seizures
  • Subject has a history of unexplained loss of consciousness or transient ischemic attack within 12 months of treatment start
  • Subject is unwilling to stop using herbal supplements that can affect the PSA, such as saw palmetto or prostate cancer (PC)-SPES
  • Subject has another active malignancy other than non-melanomatous skin cancer (unless it is metastatic) or superficial bladder cancer
  • Must not have a gastrointestinal condition that would interfere with absorption
  • Subjects may not be on other therapies that affect hormone levels, such as estrogens, testosterones, ketoconazole during this study; however, megestrol for hot flashes is permitted

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02522715


Locations
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United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Julie N. Graff    503-220-8262 ext 55688    graffj@ohsu.edu   
Principal Investigator: Julie N. Graff         
Portland Veterans Administration Medical Center Recruiting
Portland, Oregon, United States, 97239
Contact: Julie N. Graff    503-220-8262 ext 55688    graffj@ohsu.edu   
Principal Investigator: Julie N. Graff         
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Heather H. Cheng    800-804-8824    hhcheng@u.washington.edu   
Principal Investigator: Heather H. Cheng         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Julie Graff OHSU Knight Cancer Institute

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Responsible Party: Julie Graff, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02522715     History of Changes
Other Study ID Numbers: IRB00011227
NCI-2015-01103 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
11227
CRS00001390
IRB00011227 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( U.S. NIH Grant/Contract )
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Cortisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents