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

NCT02522715 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB00011227NCI-2015-0110311227CRS00001390
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

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.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Dose Limiting ToxicitiesGgraded by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (Phase I)

  The percentage of participants will be reported with 95% confidence interval using exact method.

  Up to 42 days

• PSA Response 1, Defined as >= 90% PSA Decline From Baseline

  The percentage of participants with a \>= 90% PSA decline from baseline will be reported with 95% confidence interval using exact method. 'PSA response' is based on Prostate Cancer Working Group 2's (PCWG2) recommendations, which do not offer a specific definition as no single degree of decline has been established.

  Baseline to time of >= 90% PSA decline, assessed up to 68 weeks

Secondary Outcomes (7)

• Incidence of Adverse Events Graded by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0

  Up to 28 days after the last dose of study medication

• Overall Survival

  Up to 5 years

• Pharmacokinetic Parameters of Cabazitaxel: Max Plasma Concentration (Cmax)

  Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of cycles 1 and 2 (each cycle is 21 days)

• Pharmacokinetic Parameters of Cabazitaxel: Mean Area Under the Curve (AUC)

  Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of cycles 1 and 2 (each cycle is 21 days)

• Pharmacokinetic Parameters of Cabazitaxel: Mean Cabazitaxel Half-Life

  Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of cycles 1 and 2 (each cycle is 21 days)

Study Arms (1)

Treatment (cabazitaxel, enzalutamide)

EXPERIMENTAL

Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles 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; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Prednisone

Interventions

Cabazitaxel DRUG

Given IV

Also known as: Jevtana, RPR-116258A, Taxoid XRP6258, XRP-6258

Treatment (cabazitaxel, enzalutamide)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (cabazitaxel, enzalutamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabazitaxel, enzalutamide)

Pharmacological Study OTHER

Correlative studies

Treatment (cabazitaxel, enzalutamide)

Prednisone DRUG

Given PO

Also known as: .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, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (cabazitaxel, enzalutamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (3)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Portland VA Medical Center

Portland, Oregon, 97239, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; XRP6258; enzalutamide; Prednisone; deltacortene; prednylidene

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Rachel Slottke, Program Manager
• Organization: Oregon Health & Science University

slottker@ohsu.edu

503-494-6117

Study Officials

• Julie N Graff

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2015
• First Posted: August 13, 2015
• Study Start: August 13, 2015
• Primary Completion: October 16, 2019
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 24, 2026
• Results First Posted: December 23, 2020

Record last verified: 2026-02

Locations

US (3)