Overview

PROstate Cancer TReatment Optimization Via Analysis of Circulating Tumour DNA

Status:
Recruiting
Trial end date:
2024-12-01
Target enrollment:
0
Participant gender:
Male
Summary
The purpose of this study is to assess the strategy in treatment selection using ctDNA fraction as a predictive biomarker to direct treatment decision (ctDNA fraction <2% receives enzalutamide, and ctDNA fraction ≥2% receives docetaxel) versus clinician's choice of enzalutamide or docetaxel, in subjects with metastatic castration-resistant prostate cancer post abiraterone setting.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
British Columbia Cancer Agency
Treatments:
Docetaxel
Criteria
INCLUSION CRITERIA

Patients must meet ALL of the following criteria:

1. Willing and able to provide informed consent

2. Adult males ≥ 18 years age

3. History of histologically confirmed adenocarcinoma of the prostate without evidence of
neuroendocrine or small cell differentiation. If histology is not available, patients
must have metastatic disease typical of prostate cancer (i.e., involving bone or
pelvic lymph nodes or para-aortic lymph nodes) AND a serum concentration of PSA that
is rising and >20ng/mL at the time prostate cancer was diagnosed clinically

4. Consent to analysis of archival tissue collected at diagnosis is mandatory

5. Prior surgical orchiectomy or if on LHRH agonist/antagonist then testosterone < 1.7
nmol/L at screening visit (patients must maintain LHRH agonist/antagonist therapy for
duration of study treatment if not surgically castrated)

6. Evidence of metastatic disease on bone scan or CT scan

7. Evidence of biochemical or imaging progression in the setting of surgical or medical
castration while on abiraterone. Progressive disease for study entry is defined by one
of the following three criteria as per PCWG317:

1. PSA progression: minimum of two rising PSA values from a baseline measurement of
one week interval. Minimum PSA at screening visit is 1.0 ng/mL

2. Soft tissue or visceral disease progression: an increase ≥20% in the sum of the
diameter (short axis for nodal lesions and long axis for non-nodal lesions) from
the smallest sum of the diameter since treatment started, or appearance of any
new lesions (see Appendix B for definition of measurable disease as per RECIST
1.1 criteria).

3. Bone progression: ≥ 2 new lesions on bone scan confirmed on subsequent bone scan
at least 8 weeks apart (2+2 rule as per PCWG317)

8. ECOG performance status 0-2 (see Appendix C)

9. Prior treatment with abiraterone, in either castration-sensitive or
castration-resistant setting.

10. Eligible for treatment with either enzalutamide or docetaxel as per standard of care
guidelines

11. Adequate organ function defined as:

1. Absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L and
hemoglobin ≥ 90 g/L

2. Creatinine clearance ≥ 30 ml/min (calculated by Cockcroft-Gault formula, see
Appendix D)

3. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with
known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)

4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN

12. Able to swallow study drug and comply with study requirements including provision of
peripheral blood samples at specified time points for correlative studies

13. Recovery from all prior treatment-related toxicity to grade ≤ 2 (as per CTCAE 5.0)

EXCLUSION CRITERIA

Patients must NOT meet any of the following criteria:

1. Severe concurrent illness or co-morbid disease that would make the subject unsuitable
for enrolment

2. Prior therapy with enzalutamide or other experimental anti-androgens (e.g. ARN-509,
TOK-001)

3. Prior systemic chemotherapy with docetaxel or cabazitaxel

4. Active concurrent malignancy (with the exception of non-melanomatous skin cancer, or
other solid tumours curatively treated with no evidence of disease for ≥3 years)

5. Wide-field radiotherapy or radioisotopes such as Strontium-89, or Radium-223 ≤ 28 days
prior to starting study drug (limited-field palliative radiotherapy for up to 5
fractions prior to starting study drug is permitted)

6. Brain metastases or active epidural disease (treated epidural disease is permitted)

7. Contraindication to prednisone therapy including poorly controlled diabetes mellitus

8. History of seizure or seizure disorder, or history of any cerebrovascular event within
6 months of study entry.

9. Uncontrolled hypertension Grade ≥3 (i.e. systolic blood pressure ≥160 mmHg or
diastolic blood pressure ≥100 mmHg)

10. Gastrointestinal disorder affecting absorption

11. Major surgery within 4 weeks of starting study treatment