Clinical Trial to Test Efficacy of Targeting Hypoxia Combined With ARSI After First-line ARSI Therapy for Castrate Resistant Prostate Cancer

Launched by UNIVERSITY HEALTH NETWORK, TORONTO · Feb 18, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for men with castration-resistant prostate cancer (CRPC) that has spread to other parts of the body. Specifically, the trial is testing a drug called evofosfamide combined with a different type of hormone therapy after patients have already received one type of hormone therapy that didn’t work. Participants will first have some imaging tests to see the extent of their cancer, and then they will receive evofosfamide through an IV on specific days every month, along with the new hormone therapy. The goal is to see if this combination is effective in slowing down the cancer.

To participate in this trial, men need to be at least 18 years old and have been diagnosed with advanced CRPC that has progressed after initial treatments. They must also be receiving ongoing hormone therapy to keep testosterone levels low. Participants will have regular check-ups to monitor their health and the cancer's response to the treatment. This trial is currently not recruiting, but it will be important for potential participants to discuss any other health conditions they have with their doctor to ensure they meet all eligibility requirements.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • 1. At least 18 years of age;
• • 2. Ability to understand the purposes and risks of the trial and has signed a written ICF approved by the investigator's REB;
• • 3. CRPC stage M1 based on conventional imaging (CT and/or bone scan) or PSMA PET;
• • 4. Progression (i.e., PSA rise of 25% or more, and absolute increase of 2 ng/mL or more from the nadir) to first-line ARSIs (Abi or Enza or Daro or Apa monotherapy) and subsequent docetaxel or deemed ineligible for it;
• • 5. Ongoing castration therapy (e.g., surgical or medical with LHRH agonists/antagonist), with baseline testosterone level \<50ng/dL;
• • 6. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2;
• • 7. In subjects with known significant pulmonary disease (severe chronic obstructive or other pulmonary disease with hypoxemia), measure oxygen saturation using pulse oximeter after a 2-minute walk. Subjects must have oxygen saturation ≥90% to be eligible for the trial.
• Exclusion Criteria:
• * 1. ANC \<1,000/mm3, and/or hemoglobin \<9.0 g/dL, and/or platelet count \<100,000/mm3; independent of transfusion and/or growth factors 2. Liver dysfunction: total bilirubin, serum glutamic oxaloacetic transaminase (SGOT; aspartate aminotransferase \[AST\]) and/or serum glutamic-pyruvic transaminase (SGPT; alanine aminotransferase \[ALT\]) \>1.5 × upper normal limit (UNL); 3. Inadequate renal function: creatinine \>1.5 × UNL, or eGFR \<40 mL/min; 4. Any Grade 3 or greater toxicity experienced during treatment with prior ARSI; 5. Severe, active co-morbidity defined as follows:
• • 1. Myocardial infarction within 6 months prior to date of enrollment.
• • 2. Current severe or unstable angina.
• • 3. New York Heart Association Functional Classification III/IV. (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
• • 4. Severe chronic obstructive or other pulmonary disease with hypoxemia at rest (requires supplementary oxygen, symptoms due to hypoxemia).
• • 5. History of any condition that in the opinion of the investigator, would preclude participation in this study.
• • 6. Known liver metastases based on conventional imaging (i.e., abdominal CT and/or MR).
• • 7. Known brain, leptomeningeal or epidural metastases (unless treated, well controlled, and not requiring steroidal therapy for at least 3 months).
• • 8. Major surgery (other than diagnostic surgery), open biopsy, or significant traumatic injury, ≤28 days prior to the date of signing informed consent. Subject must have completely recovered from surgery.
• • 9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• • 10. Treatment of PCa with radiation therapy or surgery ≤28 days prior to the Cycle 1 Day 1.
• • 11. Prior therapy with a hypoxic cytotoxin. 12. HIV-infected patients with detectable viral load and/or on effective anti-retroviral therapy (ART) with undetectable viral load for less than 6 months. Note: HIV testing is not required for eligibility for this protocol. Drug-drug interactions with ART occur via many mechanisms, with cytochrome P450 CYP3A4-mediated interactions being the most common. Patients who are using concurrent strong or moderate CYP3A4 inhibitors (e.g., ritonavir, cobicistat) or strong or moderate CYP3A4 inducers must be switched to an alternate effective ART regimen ≥4 weeks before study enrollment or should be excluded from the study if their regimen cannot be altered.
• • 13. Active infection with hepatitis B or hepatitis C (i.e., detectable viral load) with or without active treatment in patients with previously known infection. Note: Only Hepatitis B testing is required for eligibility for this protocol as per standard practice prior to systemic therapy.
• • 14. Subjects who have exhibited allergic reactions to a structural compound similar to evofosfamide or the drug product excipients.
• • 15. Subjects who are taking medications that prolong QT interval and have a risk of Torsades de Pointes (see Appendix A).
• • 16. Subjects with a QTc interval calculated according to Fridericia formula (QTC = QT / RR1/3) of \>450 msec based on screening electrocardiogram (ECG).
• • 17. Subjects with a history of long QT syndrome. 18. Subjects taking a medication that is a moderate or strong inhibitor or inducer of CYP3A4within 14 days or 5 half-lives (whichever is longer) prior to signing of ICF. (see Appendix B).
• • 19. Subjects taking a medication that is a sensitive substrate or substrates with a narrow therapeutic index of CYP3A4, CYP2D6, or CYP2C9 (see Appendix C).
• • 20. Any other significant concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this trial.
• • 21. Unwillingness or inability to comply with the study protocol for any reason.