Evaluating Hormone Therapy to Achieve Optimal Doses in Metastatic Prostate Cancer

Browse trials for

• Prostatic Neoplasms 6,353
• Neoplasm Metastasis 3,508

Keywords

• Prostate cancer
• Metastatic
• ARPI
• ADT
• Androgen Receptor Pathway Inhibitor
• Androgen Deprivation Therapy

Study arms

• Active comparator
  Control Arm

  Standard Dose = Standard recommended (100%) dose of ARPI (enzalutamide, apalutamide, darolutamide or abiraterone).

  Drug: Abiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy

• Experimental
  Interventional Arm

  Reduced Dose = Reduced dose (50%) of the standard recommended dose of ARPI (enzalutamide, apalutamide, darolutamide or abiraterone).

  Drug: Abiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy

Interventions

• DrugAbiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy

  ARPI therapy (Abiraterone, Apalutamide, Enzalutamide or Darolutamide) selected by local investigator per standard of care

  Also known as: Goserelin, Leuprolide, and Triptorelin, Degarelix or Relugolix (ADT therapy per standard of care)

Primary outcomes

1. Overall survival (primary efficacy)

   Overall survival, defined as the time from date of randomisation to date of death from any cause, and those who are alive are censored at the date last known to be alive. This will be assessed for non-inferiority using a margin for the absolute risk difference at 2 years of ≤4 percentage points, between reduced and standard dose ARPI arms. A hierarchical approach will be applied to all 3 primary outcome measures, in which each analysis (in turn) should yield a p-value of \<0.05 in the following ranked order: 1. Non-inferiority for overall survival 2. Superiority of a mean difference in QoL fatigue score (expected to be ≥7 units) 3. Superiority for the percentage of patients who do not discontinue ARPI due to adverse events

   Time frame: From randomisation up to 6 years (or date last known to be alive) or date of death, whichever occurs first.

2. The percentage of patients who permanently discontinue ARPI due to adverse events

   Adverse events will be analysed using CTCAE Version 6.0 categorisation (all grades) for patients who permanently discontinue APRI. A hierarchical approach will be applied to all 3 primary outcome measures, in which each analysis (in turn) should yield a p-value of \<0.05 in the following ranked order: 1. Non-inferiority for overall survival 2. Superiority of a mean difference in QoL fatigue score (expected to be ≥7 units) 3. Superiority for the percentage of patients who do not discontinue ARPI due to adverse events

   Time frame: From start of treatment to permanent discontinuation of trial treatment up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).

3. Fatigue assessed using the EORTC 12-point fatigue scale (primary toxicity)

   Fatigue assessed using the EORTC 12-point fatigue scale (QLQ-FA12). A hierarchical approach will be applied to all 3 primary outcome measures, in which each analysis (in turn) should yield a p-value of \<0.05 in the following ranked order: 1. Non-inferiority for overall survival 2. Superiority of a mean difference in QoL fatigue score (expected to be ≥7 units) 3. Superiority for the percentage of patients who do not discontinue ARPI due to adverse events

   Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.

Secondary outcomes

1. Toxicities using the CTCAE v6 categorisation (all grades).

   Toxicities using the CTCAE Version 6.0 categorisation (all grades). Events that would be of special interest include hypertension, rash, hot flushes, cardiovascular events, and falls.

   Time frame: From date of consent to 30 days post last IMP dose administration.

2. Failure-free survival (FFS)

   Failure-free survival (FFS) defined as the time from the date of randomisation to the date of the first of the following forms of treatment failure: biochemical (prostate-specific antigen (PSA)) failure; progression of local, lymph-node, or distant metastases; starting another line of therapy, or death from prostate cancer. Patients without an FFS event would be censored at the date last known to be alive. Stopping treatment for reasons other than the events listed above would not be considered an FFS event.

   Time frame: From randomisation until disease progression or death up to 6 years after first patient enrolled.

3. Measures of progression (rising PSA, and locally defined clinical and radiological progression), at 1 and 2 years post-randomisation.

   * Proportion of patients who have rising PSA (PSA progression is defined as ≥25% increase and at least a 2 ng/mL absolute increase above the nadir, confirmed by a second value ≥3 weeks later) at 1 and 2 years post randomisation. * Proportion of patients who have PSA only progression: PSA rise of ≥25% above lowest PSA result compared to baseline at 1 and 2 years post randomisation. * Proportion of patients who have significant clinical progression, including new cancer related symptoms, as determined by the local clinical team: at 1 and 2 years post randomisation. * Proportion of patients who have radiological progression as determined by the local clinical team: at 1 and 2 years post randomisation. * Proportion of patients who achieve PSA nadir of \<0.2 within 12 months of starting therapy (primarily for mHSPC patients).

   Time frame: From randomisation to date of documented objective disease progression, assessed up to 2 years post-randomisation.

4. Adherence: the proportion of patients who stop ARPI permanently due to reasons other than disease progression, at 1 and 2 years.

   Adherence: proportion of patients who stop ARPI permanently due to reasons other than disease progression, at 1 and 2 years (reasons will be recorded).

   Time frame: From randomisation to 2 years post-randomisation.

5. Adherence: the duration of ARPI.

   Adherence: the duration of ARPI (in months) from the time of starting therapy.

   Time frame: From start of treatment to permanent discontinuation of trial treatment up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).

6. Proportion of patients who have a dose reduction of ARPI (from their starting dose, in either arm) due to adverse events.

   Proportion of patients who have a dose reduction of ARPI (from their starting dose, in either arm) due to adverse events.

   Time frame: From start of treatment to documented dose reduction of trial treatment due to adverse events up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).

7. Proportion of patients (dose reduction arm) who have their dose increased.

   Proportion of patients (dose reduction arm) who have their dose increased (reasons will be recorded).

   Time frame: From start of treatment to permanent discontinuation of trial treatment up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).

8. Health-related quality of life using the EORTC QLQ-C30 questions

   Quality of Life assessments will be undertaken using EORTC QLQ-C30 questionnaire using Likert score (26 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much; 2 questions scored: 1-7, 1=very poor, 7=excellent). Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.

   Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.

9. Health-related quality of life using the EORTC QLQ-IL249 questions

   Quality of Life assessments will be undertaken using EORTC QLQ-C30 which will include QLQ-IL249 questions using Likert score (22 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much). Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.

   Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.

10. Health-related quality of life using the Euro-Qol-5D-5L (EQ-5D-5L)

    Quality of Life assessments will be undertaken using EQ-5D-5L (self-reported) questionnaire using a combination of Likert score (5 questions with 5 dimensions of abilities) and visual analogue score (scored 0-100, 0=worst, 100=best). Descriptions of mean change in EQ-5D-5L scores will be presented and compared to baseline values from pre-treatment.

    Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.

Individual participant data

Plan to share: No — Data will not be shared until analysed and used as part of the study at which point data access will be considered with the researchers.