Phase I Trial of PACE for Metastatic Prostate Cancer

NCT03110588 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: F161215003 (UAB 1663)
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Metastatic Prostate Cancer

Keywords

metastatic prostate cancer; castration-resistant prostate cancer; PACE (Prednisone, Abiraterone, Cabazitaxel, and Enzalutamide)

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of PACE as first-line therapy

  The maximum tolerated dose is when 6 patients are treated at a dose level with less than two patients demonstrating dose limiting toxicities. Dose limiting toxicities are defined as any grade greater than or equal to grade 3 non-hematologic toxicity (except greater than or equal to grade 2 neurotoxicity), or greater than or equal to grade 4 neutropenia or thrombocytopenia lasting longer than or equal to 7 days. Toxicities will be assessed according to the NCI Common Terminology Criteria for Adverse Events version 4.03.

  Baseline up to 2 years

Secondary Outcomes (5)

• Prostate specific antigen (PSA)

  Baseline up to 2 years

• Radiographic progression-free survival with PACE

  Baseline up to 2 years

• Progression-free survival with PACE

  Baseline up to 2 years

• Objective response rate of measurable disease

  Baseline up to 2 years

• Pain response

  Baseline up to 2 years

Study Arms (2)

PACE with Cabazitaxel @ 15 mg/m2

EXPERIMENTAL

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)

PACE with Cabazitaxel @ 20 mg/m2

EXPERIMENTAL

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)

Interventions

PACE with Cabazitaxel (15 mg/m2) DRUG

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

PACE with Cabazitaxel @ 15 mg/m2

PACE with Cabazitaxel (20 mg/m2) DRUG

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

PACE with Cabazitaxel @ 20 mg/m2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The patient must have a cancerous prostate.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histologically proven adenocarcinoma of the prostate with metastatic disease.
• 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.
• Most recent PSA ≥2 ng/ml
• Testosterone \< 50 ng/dL
• 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.
• ECOG performance status 0-1.
• 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
• 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.
• Ability to sign a written informed consent form.
• Subject is willing to stop herbal supplements.

You may not qualify if:

• Prior docetaxel for castration-resistant disease (prior docetaxel for castration-sensitive disease is allowed but not required).
• Prior enzalutamide, abiraterone, cabazitaxel.
• History of severe hypersensitivity reaction (≥grade 3) to docetaxel.
• History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs.
• Concomitant vaccination with yellow fever vaccine.
• Prior investigational androgen synthesis or androgen receptor antagonists.
• Prior hypersensitivity reaction to capsule components of enzalutamide including labrasol, butylated hydroxyanisole and butylated hydroxytoluene
• Other non-chemotherapeutic investigational agents within 14 days (prior chemotherapy needs a ≥4 week washout).
• 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).
• Prior isotope therapy with Strontium-89, Samarium or radium-223.
• Patients with a history of central nervous system metastases (brain, meninges, spinal cord).
• Imminent risk of pathologic fracture or cord compression.
• History of seizures, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months, cerebrovascular accident, and brain arteriovenous malformations.
• 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.
• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Astellas Pharma Inc: collaborator
• Sanofi: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel

Condition Hierarchy (Ancestors)

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

Study Officials

• Mansoor N Saleh, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2017
• First Posted: April 12, 2017
• Study Start: May 9, 2018
• Primary Completion: December 18, 2019
• Study Completion: December 18, 2019
• Last Updated: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)