Evofosfamide for Prostate Cancer

(EVO Trial)

Overseen By Alejandro Berlin, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Castration therapy

Must not be taking: QT prolonging drugs, CYP3A4 inhibitors

Disqualifiers: Liver metastases, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: Until disease progression or unacceptable toxicity

35 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but it mentions that participants must not take certain medications that affect the liver enzyme CYP3A4 within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

How is the drug evofosfamide unique for treating prostate cancer?

Evofosfamide is unique because it is a hypoxia-activated prodrug, meaning it becomes active in low-oxygen environments like those found in some tumors, potentially making it more effective in targeting cancer cells compared to standard treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for men with metastatic castrate-resistant prostate cancer (M1 CRPC) who have not responded to first-line ARSI treatments. Candidates should be ineligible for or have progressed after second-line Docetaxel therapy. They must undergo baseline molecular imaging and are encouraged to biopsy a dominant lesion before starting the study.

Inclusion Criteria

Ability to understand the purposes and risks of the trial and has signed a written ICF approved by the investigator's REB

My prostate cancer has spread and shows on scans.

My cancer progressed after initial hormone therapy and chemotherapy.

Exclusion Criteria

I am allergic to compounds similar to evofosfamide or its ingredients.

I am on medication that affects my heart's rhythm.

I have an active hepatitis B or C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging and Biopsy

Baseline molecular imaging (PSMA and FDG PET/CT) and optional biopsy of a dominant lesion

1-2 weeks

1 visit (in-person)

Treatment

Participants receive alternate ARSI and evofosfamide at a dose of 480 mg/m2 IV on Days 1, 8, and 15 of every 28-day cycle

Until disease progression or unacceptable toxicity

Monthly visits (in-person) for assessments

Follow-up

Participants are monitored for survival endpoints following completion of study treatment until death

Until death

Every 8 weeks (± 3 days) for assessments

Treatment Details

Interventions

• Evofosfamide

Trial Overview The trial tests evofosfamide combined with an alternate ARSI treatment in patients who failed first-line ARSIs. Evofosfamide is given intravenously on specific days of a 28-day cycle, continuing until disease progression, unacceptable toxicity, or withdrawal by the subject.

Participant Groups

Group I: Evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

ImmunoGenesis

Industry Sponsor

Trials

3

Recruited

210+

References

1. Greece pubmed.ncbi.nlm.nih.gov

Palliative chemotherapy with trofosfamide in advanced prostate cancer. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Phase II trial of ifosfamide in the treatment of metastatic hormone-refractory patients with prostatic cancer. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. [2020]

5. Japan pubmed.ncbi.nlm.nih.gov

[Reactivation of prostatic cancer and chemotherapy in reactivated prostatic cancer]. [2015]