Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamide.

A Randomized Multicenter Phase III Trial Comparing Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamide.

This is a randomized phase 3 trial aiming to compare the efficacy of docetaxel and hormone therapy as second line treatment in patients with mCRPC progressing after therapy with abiraterone or enzalutamide.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Castration-resistent Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Abiraterone Acetate or Enzalutamide

Detailed Description

Patients will be randomized 1:1 to receive docetaxel or hormone therapy (abiraterone or enzalutamide based on previous treatment).

Docetaxel (standard) will be administered for 10 cycles (maximum).

Hormone therapy (experimental) will be administered until progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Distant metastatic disease
• Previous first line treatment with abiraterone or enzalutamide for 6 cycles interrupted at least 2 weeks before randomization
• Patients must be ≥ 18 years of age
• Patients must have castrate serum level of testosterone of < 0.5 ng/mL ( 1.7 nmol/L)
• Asymptomatic or Oligosymptomatic disease
• Progressive disease according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
• ECOG performance status (PS) of 0-2
• Sexually active males must use an accepted and effective method birth control measure
• Written informed consent

Exclusion Criteria:

• Prior exposure to docetaxel or abiraterone for treatment of hormone-sensitive metastatic prostate cancer (mHSPC)
• History of adrenal insufficiency or hypoaldosteronism
• Any medical condition that would make prednisone use contraindicated
• Any medical condition that would make docetaxel use contraindicated
• Patients unable to swallow orally administered medication
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) requiring antiretroviral therapy
• Other malignancy within the last 5 years, except for adequately treated non melanoma skin cancer, bladder cancer (pTis, pTa, pT1) or other solid tumours curatively treated with no evidence of disease for > 5 years
• Participation in another clinical study with an investigational product within 30 days prior to randomization
• Persistent toxicities [>Common Terminology Criteria for Adverse Event (CTCAE) grade 1)] caused by previous cancer therapy prior to randomization
• Uncontrolled medical conditions including diabetes mellitus. Clinically significant cardiovascular disease (e.g.: uncontrolled hypertension or arrhythmia, unstable angina pectoris, congestive heart failure (CHF), vascular disease (arterial thrombosis) and myocardial infarction within < 6 months
• Left ventricular ejection fraction < 50%
• Peripheral neuropathy [> CTCAE grade 2]

• Inadequate bone marrow function defined as:

  • haemoglobin < 9.0 g/dL
  • absolute neutrophils count (ANC) <1.5 x 109/L (> 1500 per mm3)
  • platelet count <100 x 109/L (>100,000 per mm3)

• Inadequate renal and hepatic function, defined as:

  • total serum bilirubin > 1,0 x ULN
  • AST/SGOT o ALT/SGPT > 1,5 x ULN
  • calculated creatinine clearance < 40 mL/min
  • potassium level < 3,5 mmol/L
  • Child-Pugh class C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Docetaxel; Docetaxel 75 mg/m2 intravenous (iv) infusion every 3 weeks plus oral prednisone 5 mg twice daily for a maximum of 10 cycles.	Drug: Docetaxel; Docetaxel 75 mg/m2 intravenous (iv) infusion every 3 weeks plus oral prednisone 5 mg twice daily for a maximum of 10 cycles.
Experimental: Abiraterone or Enzalutamide; Patient will receive Abiraterone or Enzalutamide based on previous treatment. Abiraterone given orally at the dose of 1000 mg daily plus oral prednisone 5 mg twice daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment. Enzalutamide given orally at the dose of 160 mg daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment.	Drug: Abiraterone Acetate or Enzalutamide; Patient will receive Abiraterone or Enzalutamide based on previous treatment. Abiraterone given orally at the dose of 1000 mg daily plus oral prednisone 5 mg twice daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment. Enzalutamide given orally at the dose of 160 mg daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from randomization until death	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS is defined as the time elapsed from the date of randomization to the date of progression, as defined by investigators, or the date of death, whichever comes first.	up to 5 years
Time to Prostate-Specific Antigen (PSA) Progression	as determined by investigator	up to 5 years
Incidence of symptomatic skeletal events (SSE)	reporting the incidence and types of skeletal related events	up to 5 years
Time to symptomatic skeletal event (SSE)	Time from the date of randomization to the date of documented symptomatic skeletal event	up to 5 years
Time to Pain Progression	Time from the date of randomization to the date of pain progression	up to 5 years
Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0	graded according to Common Terminology Criteria for Adverse Event (CTCAE) version 5.0	baseline, during treatment (every 4 weeks) up to 5 years
Determination of changes in quality of life	EORTC QLQ-C30, a quality of life questionnaires, composed by 30 items graded from1 (not at all) to 4 (very much) after 1 year from the diagnosis	baseline, during treatment up to 5 years
Radiographic response (bone lesions)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	up to 5 years
Radiographic response (soft tissue lesions)	Prostate Cancer Working Group 3 (PCWG3) criteria	up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: hormone therapy; docetaxel; metastatic castration-resistent prostate cancer; asymptomatic or oligosymptomatic
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Docetaxel; Abiraterone Acetate
• Other Study ID Numbers: Meet-Uro4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No