Pimonidazole for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University Health Network, Toronto

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

Compensation: Varies

Number of Visits: 1

39 Participants Needed

Trial Summary

What is the purpose of this trial?

Prostate cancer is the most commonly diagnosed form of cancer in Canadian men. In 2006, greater than 250,000 men were diagnosed with prostate cancer in the United States and Canada with more than 32,000 men dying of their disease. Using the prognostic variables of T-category, the serum prostate specific antigen (PSA), and the pathologic Gleason score (GS), men with localized prostate cancer are placed in low, intermediate and high-risk groupings. Usually this is treated with surgery, radiation therapy, hormone therapy and/or watchful waiting (also known as active surveillance). While these treatments are quite effective, tumours are likely to recur in about 40% of cases. There is a need for additional prostate cancer treatments. To address this need, many experimental therapies are being developed and tested in mice with prostate tumors. This includes the study of aggressive prostate cancer cells such as stem cells, or Tumour Initiating Cells (TICs), or oxygen deprived cells, which may be the ones most likely to re-grow into a tumour or spread throughout the body. Researchers want to try and isolate these special cells from the prostate after surgery to study their features, and to see if they can re-grow as solid tumours in mice. Researchers would like to test whether the prostate cancer stem cells are more resistant or less resistant to treatments. This will allow researchers to study and test new treatments that specifically target resistant and aggressive prostate cancer cells. The investigators hypothesize that marker-defined TIC cells or hypoxic cancer cells have unique genetics in primary prostate cancers and are relatively chemo- and radio-resistant.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How does the drug Pimonidazole differ from other prostate cancer treatments?

Pimonidazole is unique because it targets PIM1 kinase, which is involved in prostate cancer development and resistance to standard treatments like docetaxel. By inhibiting PIM1, this drug may help overcome resistance and improve treatment effectiveness in prostate cancer. ^{1 2 3 4 5}

Research Team

Alejandro Berlin, MD.

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for men with intermediate to high-risk prostate cancer who are set to have surgery at Princess Margaret Cancer Centre-UHN. They should have a Gleason score of 7 with more than half of biopsies showing tumor, or score 8+. The cancer must be adenocarcinoma and not spread beyond the prostate (T2-T3 N0 M0). Men can't join if they can't take pimonidazole tablets or if their cancer has spread further (T4, N1, M1) or isn't adenocarcinoma.

Inclusion Criteria

My prostate cancer is classified as adenocarcinoma.

I have prostate cancer and will have surgery at Princess Margaret Cancer Centre-UHN.

My cancer is in stage T2-T3, has not spread to lymph nodes or other parts of the body.

Exclusion Criteria

My cancer is not adenocarcinoma.

You are not able to swallow pimonidazole tablets.

My cancer has spread to nearby or distant parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo radical prostatectomy to obtain specimens for analysis

1 day

1 visit (in-person)

Laboratory Analysis

Specimens are analyzed for pimonidazole staining and tumor initiating cells

3 years

Follow-up

Participants are monitored for biochemical failure and other outcomes

3 years

Treatment Details

Interventions

• Pimonidazole

Trial Overview The study is testing Pimonidazole in patients undergoing surgery for prostate cancer. It aims to isolate aggressive cancer cells from removed prostates to see how they behave and respond to treatments when grown in mice. This could help develop therapies targeting resistant prostate cancer cells.

Participant Groups

Group I: Pimonidazole Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

PIM1 kinase as a target in prostate cancer: roles in tumorigenesis, castration resistance, and docetaxel resistance. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Correlation between the expression of Pim-1 and androgen-deprivation therapy for prostate cancer]. [2018]

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

The discovery and optimization of aminooxadiazoles as potent Pim kinase inhibitors. [2015]

4. France pubmed.ncbi.nlm.nih.gov

Discovery of PIM-1 kinase inhibitors based on the 2,5-disubstituted 1,3,4-oxadiazole scaffold against prostate cancer: Design, synthesis, in vitro and in vivo cytotoxicity investigation. [2023]

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

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer. [2018]