Phase I Trial of PACE for Metastatic Prostate Cancer

NCT ID: NCT03110588

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-09
• Study Completion Date: 2019-12-18

Brief Summary

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).

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.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

PACE with Cabazitaxel (15 mg/m2)

Intervention Type: DRUG

Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 15 mg/m2.

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.

Group Type: EXPERIMENTAL

PACE with Cabazitaxel (20 mg/m2)

Intervention Type: DRUG

Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 20 mg/m2.

Interventions

PACE with Cabazitaxel (15 mg/m2)

Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 15 mg/m2.

Intervention Type: DRUG

PACE with Cabazitaxel (20 mg/m2)

Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 20 mg/m2.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mansoor N Saleh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

F161215003 (UAB 1663)

Identifier Type: -

Identifier Source: org_study_id