Clinical trial NCT04139772: 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.
Official title: 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: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Metastatic Castration-resistent Prostate Cancer
Keywords: metastatic castration-resistent prostate cancer
asymptomatic or oligosymptomatic
hormone therapy
docetaxel
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2019-10-25
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment Comparative Randomized Phase 3 Design
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: up to 5 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: up to 5 years
measure: Time to Prostate-Specific Antigen (PSA) Progression
timeFrame: up to 5 years
measure: Incidence of symptomatic skeletal events (SSE)
timeFrame: up to 5 years
measure: Time to symptomatic skeletal event (SSE)
timeFrame: up to 5 years
measure: Time to Pain Progression
timeFrame: up to 5 years
measure: Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0
timeFrame: baseline, during treatment (every 4 weeks) up to 5 years
measure: Determination of changes in quality of life
timeFrame: baseline, during treatment up to 5 years
measure: Radiographic response (bone lesions)
timeFrame: up to 5 years
measure: Radiographic response (soft tissue lesions)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
Study officials:
affiliation: National Cancer Institute, Naples
name: Sandro Pignata, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Gaetano Facchini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Francesco Perrone, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oncology Department, Ospedale Santa Chiara, Trento
name: Orazio Caffo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Clorinda Schettino, MD
role: STUDY_CHAIR
References: