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

NCT06836726 | Not Yet Recruiting Phase 2

• 1 other identifier: 24-6044
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-institution, single-arm, open-label Phase 2 trial evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs. In those progressing after second-line Docetaxel or deemed ineligible to it, the use of alternate ARSI remains the most common line of therapy in our Province, in keeping with recent international recommendations. After baseline molecular imaging (PSMA and fluorodeoxyglucose (FDG) PET/CT), prior to evofosfamide initiation, subjects will be encouraged to undergo biopsy of a dominant lesion: FDG-, PSMA-uptake and/or conventional imaging determined (in order, and according to feasibility). Subjects will then receive the alternate ARSI (i.e., different from the one received in first line) as per current standard practice and Provincial drug plan coverage. Additionally, subjects will receive combinatorial evofosfamide at a dose of 480 mg/m2 intravenously (IV) over 60 minutes on Days 1, 8 and 15 of every 28-day cycle. Therapy will continue until disease progression, unacceptable toxicity as a result of evofosfamide, or subject withdrawal. Assessments during evofosfamide treatment will include history, physical exam, and blood tests at each monthly visit to monitor for toxicity. Response and progression will be evaluated by whole-body PSMA PET/CT scan every 8 weeks (± 3 days) and determined using (PE)RECIST v1.1 criteria. PSA, NE markers (e.g., Serum CHGA, NSE), organ function tests (e.g., liver, kidney) and investigational liquid biopsy samples will be followed every cycle (monthly). FDG PET/CT will be performed at baseline, at 6-10 weeks from the date of signing the informed consent form (ICF), and upon progression, irrespective of treatment discontinuation or initiation of another therapy. Subjects will be followed for survival endpoints following completion of this study treatment until death.

Conditions

Castration Resistant Prostate Cancer

Keywords

CRPC; Castration Resistant Prostate Cancer; ARSIs; androgen receptor signal inhibitors

Outcome Measures

Primary Outcomes (1)

• Preliminary clinical efficacy measures of evofosfamide in subjects with CRPC progressing to first-line ARSIs +/- docetaxel

  Preliminary clinical efficacy measures of evofosfamide in subjects with CRPC (Castrate Resistant Prostate Cancer) progressing to first-line ARSIs (Androgen Receptor Signaling Inhibitor) +/- docetaxel will be determined. This is measured by the biochemical response rate (if the PSA (tumor marker) declined ≥50% compared to baseline). Sample(s) may be drawn with serum biochemistry sample(s).

  Every 8 weeks (± 3 days) until death

Secondary Outcomes (6)

• Radiological (morphological and molecular) response rates

  Every 8 weeks (± 3 days) until death

• Professional free survival (PFS)

  Every 8 weeks (± 3 days) until death

• Response rate and PFS (progression free survival) to subsequent therapies (PFS2)

  Every 8 weeks (± 3 days) until death

• OS (overall survival)

  Every 8 weeks (± 3 days) until death

• Changes in tumor biopsies

  Every 8 weeks (± 3 days) until death

Study Arms (1)

Evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs

EXPERIMENTAL

After baseline molecular imaging (PSMA and fluorodeoxyglucose (FDG) PET/CT), prior to evofosfamide initiation, subjects will be encouraged to undergo biopsy of a dominant lesion: FDG-, PSMA-uptake and/or conventional imaging determined (in order, and according to feasibility). Subjects will then receive the alternate ARSI (i.e., different from the one received in first line) as per current standard practice and Provincial drug plan coverage. Additionally, subjects will receive combinatorial evofosfamide at a dose of 480 mg/m2 intravenously (IV) over 60 minutes on Days 1, 8 and 15 of every 28-day cycle. Therapy will continue until disease progression, unacceptable toxicity as a result of evofosfamide, or subject withdrawal. Assessments during evofosfamide treatment will include history, physical exam, and blood tests at each monthly visit to monitor for toxicity. Subjects will be followed for survival endpoints following completion of this study treatment until death.

Drug: Evofosfamide

Interventions

Evofosfamide DRUG

This study is evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs.

Evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age;
• Ability to understand the purposes and risks of the trial and has signed a written ICF approved by the investigator's REB;
• CRPC stage M1 based on conventional imaging (CT and/or bone scan) or PSMA PET;
• 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;
• Ongoing castration therapy (e.g., surgical or medical with LHRH agonists/antagonist), with baseline testosterone level \<50ng/dL;
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2;
• 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.

You may not qualify if:

• \. 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:
• Myocardial infarction within 6 months prior to date of enrollment.
• Current severe or unstable angina.
• 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.)
• Severe chronic obstructive or other pulmonary disease with hypoxemia at rest (requires supplementary oxygen, symptoms due to hypoxemia).
• History of any condition that in the opinion of the investigator, would preclude participation in this study.
• \. Known liver metastases based on conventional imaging (i.e., abdominal CT and/or MR).
• \. Known brain, leptomeningeal or epidural metastases (unless treated, well controlled, and not requiring steroidal therapy for at least 3 months).
• \. 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.
• \. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• \. Treatment of PCa with radiation therapy or surgery ≤28 days prior to the Cycle 1 Day 1.
• \. 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.
• \. 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.
• \. Subjects who have exhibited allergic reactions to a structural compound similar to evofosfamide or the drug product excipients.
• \. Subjects who are taking medications that prolong QT interval and have a risk of Torsades de Pointes (see Appendix A).

Sponsors & Collaborators

• University Health Network, Toronto: lead
• ImmunoGenesis: collaborator

Study Sites (1)

Princess Margaret Cancer Center

Toronto, Ontario, M7A 2S4, Canada

Location

MeSH Terms

Interventions

TH 302

Central Study Contacts

Alejandro Berlin, MD

CONTACT

416-946-4501; Alejandro.Berlin@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-institution, single-arm, open-label Phase 2 trial evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs.

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 20, 2025
• Study Start (Estimated): May 27, 2026
• Primary Completion (Estimated): May 27, 2028
• Study Completion (Estimated): May 27, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

CA (1)