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Phase I Trial of PACE for Metastatic Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03110588
Recruitment Status : Recruiting
First Posted : April 12, 2017
Last Update Posted : September 12, 2019
Sponsor:
Collaborators:
Astellas Pharma Inc
Sanofi
Information provided by (Responsible Party):
Mansoor Saleh, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE April 7, 2017
First Posted Date  ICMJE April 12, 2017
Last Update Posted Date September 12, 2019
Actual Study Start Date  ICMJE July 1, 2018
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
Maximum tolerated dose of PACE as first-line therapy [ Time Frame: Baseline up to 2 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03110588 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
  • Prostate specific antigen (PSA) [ Time Frame: Baseline up to 2 years ]
    PSA with a greater than or equal to 30% result within 12 weeks from baseline or the previous result and maximum declines at any time during the study progression. PSA will be tested at least every 3 weeks.
  • Radiographic progression-free survival with PACE [ Time Frame: Baseline up to 2 years ]
    Radiographic examination is performed every 12 weeks to determine if there is disease progression.
  • Progression-free survival with PACE [ Time Frame: Baseline up to 2 years ]
    Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
  • Objective response rate of measurable disease [ Time Frame: Baseline up to 2 years ]
    Response will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Target lesions should be selected based on size (lesions with the longest diameter) and their suitability for accurate repeated measurements. A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD, which will be used to characterize the objective tumor response.
  • Pain response [ Time Frame: Baseline up to 2 years ]
    The Patient Pain Index (0-5 scale) is used to measure pain per cycle. A decline of greater than or equal to 2 is defined as pain response.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Trial of PACE for Metastatic Prostate Cancer
Official Title  ICMJE Phase I Trial of Prednisone, Abiraterone, Cabazitaxel and Enzalutamide (PACE) for Metastatic Castration-resistant Prostate Cancer (mCRPC)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Prostate Cancer
Intervention  ICMJE
  • Drug: PACE with Cabazitaxel (15 mg/m2)
    Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 15 mg/m2.
  • Drug: PACE with Cabazitaxel (20 mg/m2)
    Prednisone, Abiraterone, and Enzalutamide are administered orally; Cabazitaxel is be administered intravenously @ 20 mg/m2.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: PACE with Cabazitaxel (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.
    Intervention: Drug: PACE with Cabazitaxel (20 mg/m2)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 7, 2017)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2023
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: The patient must have a cancerous prostate.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mansoor N Saleh, MD 205-996-4673 mns@uab.edu
Contact: Alfreda Lewis 205-975-9025 FredaLewis@uab.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03110588
Other Study ID Numbers  ICMJE F161215003 (UAB 1663)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mansoor Saleh, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE
  • Astellas Pharma Inc
  • Sanofi
Investigators  ICMJE
Principal Investigator: Mansoor N Saleh, MD University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP