Optimizing prostate cancer treatment using blood tests

A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients with Advanced Prostate Cancer Post Abiraterone

This study is testing if using blood tests to guide treatment choices can help men with advanced prostate cancer feel better compared to standard treatment options.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: British Columbia Cancer Agency (other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 7 sites (Kelowna, British Columbia and 6 other locations)
• Trial ID: NCT04015622 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to improve treatment selection for patients with metastatic castration-resistant prostate cancer by using circulating tumor DNA (ctDNA) as a predictive biomarker. Patients will be randomly assigned to receive either biomarker-directed therapy, where treatment is based on ctDNA levels, or clinician's choice of treatment with enzalutamide or docetaxel. The study will assess the effectiveness of this personalized approach compared to standard treatment options. Patients will have the opportunity to switch therapies upon disease progression.

Who should consider this trial

Good fit: Ideal candidates include adult males aged 18 and older with histologically confirmed metastatic castration-resistant prostate cancer who have previously undergone treatment with abiraterone.

Not a fit: Patients with neuroendocrine or small cell differentiation of prostate cancer or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and personalized treatment options for patients with advanced prostate cancer.

How similar studies have performed: Other studies utilizing ctDNA as a biomarker for treatment selection have shown promise, suggesting that this approach may be effective.

Eligibility 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) ≤ 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 (with the exception of: patients who were treated with docetaxel for castration sensitive disease and did not progress for at least 12 months after completion of docetaxel)
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

Where this trial is running

Kelowna, British Columbia and 6 other locations

• BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre) — Kelowna, British Columbia, Canada (RECRUITING)
• BC Cancer - Centre for the North — Prince George, British Columbia, Canada (RECRUITING)
• BC Cancer - Surrey Centre — Surrey, British Columbia, Canada (RECRUITING)
• Sunnybrook Health Sciences Centre — Toronto, British Columbia, Canada (RECRUITING)
• BC Cancer - Vancouver Centre — Vancouver, British Columbia, Canada (RECRUITING)
• BC Cancer - Victoria Centre — Victoria, British Columbia, Canada (ACTIVE_NOT_RECRUITING)
• London Health Sciences Centre — London, Ontario, Canada (RECRUITING)

Study contacts

• Study coordinator: Corinne Maurice-Dror, MD

Conditions: Metastatic Castration-Resistant Prostate Cancer, circulating tumor DNA, Enzalutamide, Docetaxel