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.

Overview

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.

Full Title of Study: “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.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 1, 2024

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.

Interventions

  • 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.
  • 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.

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • Progression free survival (PFS)
    • Time Frame: up to 5 years
    • 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.
  • Time to Prostate-Specific Antigen (PSA) Progression
    • Time Frame: up to 5 years
    • as determined by investigator
  • Incidence of symptomatic skeletal events (SSE)
    • Time Frame: up to 5 years
    • reporting the incidence and types of skeletal related events
  • Time to symptomatic skeletal event (SSE)
    • Time Frame: up to 5 years
    • Time from the date of randomization to the date of documented symptomatic skeletal event
  • Time to Pain Progression
    • Time Frame: up to 5 years
    • Time from the date of randomization to the date of pain progression
  • Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0
    • Time Frame: baseline, during treatment (every 4 weeks) up to 5 years
    • graded according to Common Terminology Criteria for Adverse Event (CTCAE) version 5.0
  • Determination of changes in quality of life
    • Time Frame: baseline, during treatment up to 5 years
    • 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
  • Radiographic response (bone lesions)
    • Time Frame: up to 5 years
    • Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Radiographic response (soft tissue lesions)
    • Time Frame: up to 5 years
    • Prostate Cancer Working Group 3 (PCWG3) criteria

Participating in This Clinical Trial

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

Gender Eligibility: Male

Male patients with metastatic castration resistent prostate cancer

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Cancer Institute, Naples
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Sandro Pignata, MD, PhD, Principal Investigator, National Cancer Institute, Naples
    • Gaetano Facchini, MD, Principal Investigator, National Cancer Institute, Naples
    • Francesco Perrone, MD, PhD, Principal Investigator, National Cancer Institute, Naples
    • Orazio Caffo, MD, Principal Investigator, Oncology Department, Ospedale Santa Chiara, Trento
    • Clorinda Schettino, MD, Study Chair, National Cancer Institute, Naples
  • Overall Contact(s)
    • Sandro Pignata, MD, PhD, +39 081 590 3637, s.pignata@istitutotumori.na.it

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.