Purpose

This trial is being conducted to determine the feasibility and recommended dose of the combination of four drugs (prednisone, abiraterone, cabazitaxel and enzalutamide (PACE) as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Age ≥18 years 2. Histologically proven adenocarcinoma of the prostate with metastatic disease. 3. Progressive disease following androgen deprivation therapy; Prostate Specific Antigen (PSA) progression defined as baseline increase followed by any PSA increase greater than or equal to 1 week apart. 4. Most recent PSA ≥2 ng/ml 5. Testosterone < 50 ng/dL 6. Anti-androgen withdrawal of first generation AR inhibitors (bicalutamide, nilutamide) is required for 6 weeks if previous duration of stability on them was ≥3 months. 7. ECOG performance status 0-1. 8. Adequate organ function as defined below: ANC 1,500/µl; Hemoglobin 10 g/dL; Platelet count 100,000/µL; Creatinine clearance ≥45 ml/min; Potassium >3.5 mmol/L (or within institutional normal range) Bilirubin ≤ ULN (unless documented Gilbert's disease); SGOT (AST) 1.5 x ULN; SGPT (ALT) 1.5 x ULN 9. Subject agrees to use a double barrier method of contraception during the course of study therapy and for at least 3 months after completion of therapy. A double barrier method involves the use of a condom in combination one of the following: sponge, diaphragm, cervical ring with spermicidal gel or foam. Subjects who have had a vasectomy ≥6 months prior to trial therapy and those with female sexual partners who are 55 years old and post-menopausal for 2 years or sterile (by tubectomy, hysterectomy, bilateral oophorectomy) need to agree to use at least a condom. 10. Ability to sign a written informed consent form. 11. Subject is willing to stop herbal supplements.

Exclusion Criteria

  1. Prior docetaxel for castration-resistant disease (prior docetaxel for castration-sensitive disease is allowed but not required). 2. Prior enzalutamide, abiraterone, cabazitaxel. 3. History of severe hypersensitivity reaction (≥grade 3) to docetaxel. 4. History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs. 5. Concomitant vaccination with yellow fever vaccine. 6. Prior investigational androgen synthesis or androgen receptor antagonists. 7. Prior hypersensitivity reaction to capsule components of enzalutamide including labrasol, butylated hydroxyanisole and butylated hydroxytoluene 8. Other non-chemotherapeutic investigational agents within 14 days (prior chemotherapy needs a ≥4 week washout). 9. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments). 10. Prior isotope therapy with Strontium-89, Samarium or radium-223. 11. Patients with a history of central nervous system metastases (brain, meninges, spinal cord). 12. Imminent risk of pathologic fracture or cord compression. 13. History of seizures, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months, cerebrovascular accident, and brain arteriovenous malformations. 14. Uncontrolled severe intercurrent illness or medical conditions including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, uncontrolled diabetes mellitus, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction. 15. Patients with a "currently active" second malignancy other than non- melanoma skin or superficial urothelial cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered without evidence of disease for 3 years.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
The first cohort will administer the following to three patients: prednisone 5 mg orally twice daily, abiraterone 1000 mg orally once daily, enzalutamide 160 mg orally once daily, and cabazitaxel intravenous infusion at 15 mg/m2 every 3 weeks. If there are no dose limiting toxicities, the cabazitaxel will be escalated to 20 mg/m2 in a second cohort. The other three drugs will remain at the same dose.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PACE with Cabazitaxel @ 15 mg/m2
The drugs to be administered are: prednisone 5 mg orally twice daily, abiraterone 1000 mg orally once daily, enzalutamide 160 mg orally once daily, and cabazitaxel intravenous infusion at 15 mg/m2 every 3 weeks.
  • Drug: PACE with Cabazitaxel (15 mg/m2)
    Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 15 mg/m2.
Experimental
PACE with Cabazitaxel @ 20 mg/m2
The drugs to be administered are: prednisone 5 mg orally twice daily, abiraterone 1000 mg orally once daily, enzalutamide 160 mg orally once daily, and cabazitaxel intravenous infusion at 20 mg/m2 every 3 weeks.
  • Drug: PACE with Cabazitaxel (20 mg/m2)
    Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 20 mg/m2.

More Details

Status
Withdrawn
Sponsor
University of Alabama at Birmingham

Study Contact

Detailed Description

Multiple agents have been shown to improve survival in patients with mCRPC by up to five months. The combination of prednisone, abiraterone, cabazitaxel and enzalutamide may be anticipated to be feasible therapy with minimal or no adverse drug interactions. This is a phase I trial to study the feasibility of the proposed therapy. Patients will undergo a combination of oral daily drug intake at varying doses over a period of three weeks. Monitoring including blood collection for laboratory testing will be done on Day 1 of each three-week cycle with additional monitoring during the first cycle. Imaging and correlative studies will be done every 12 weeks. Therapy will continue until disease progression or severe toxicities.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.