Durvalumab +/- Tremelimumab for Prostate Cancer

No longer recruiting at 10 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must be taking: LHRH therapy

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Other malignancies, Brain metastases, Autoimmune disorders, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of durvalumab (an immunotherapy drug) alone or with tremelimumab (another immunotherapy drug) for prostate cancer that no longer responds to standard hormone therapy. The study aims to determine if these treatments can manage the cancer and identify any side effects. Men with prostate cancer that continues to grow despite low testosterone levels might be suitable candidates. The goal is to improve treatment options for advanced prostate cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking anti-androgens at least 4 weeks before starting, and you must continue LHRH therapy if you haven't had an orchiectomy. Some medications like systemic corticosteroids are allowed if not used for prostate cancer treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that durvalumab is generally safe for patients with various solid cancers. When combined with tremelimumab, it remains quite tolerable, and in many cases, this combination has demonstrated an improved safety profile.

Studies on the combination of durvalumab and tremelimumab have focused on its safety, particularly for prostate cancer. Reports suggest that side effects can be managed, although some patients have experienced adverse reactions. Overall, the combination is considered safe enough for further testing in clinical trials.

Prospective participants should find it reassuring that both treatments have shown a tolerable safety profile in past studies. However, discussing all potential risks and benefits with the medical team conducting the trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Durvalumab and Tremelimumab represent a new approach to fighting prostate cancer. Unlike traditional treatments that often involve hormone therapy or chemotherapy, both drugs are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells more effectively. Durvalumab targets the PD-L1 protein, which can hide cancer cells from immune detection, while Tremelimumab targets the CTLA-4 protein, providing another pathway to boost immune response against cancer. These mechanisms offer a promising alternative to existing therapies, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that durvalumab effectively treats various solid cancers. Studies have found that patients treated with durvalumab live longer without their cancer worsening and have improved overall survival. In this trial, some participants will receive durvalumab alone, while others will receive a combination of durvalumab and tremelimumab. When used with tremelimumab, durvalumab can yield even better results. Specifically, 30.7% of patients using this combination were still alive after 36 months. These treatments enhance the immune system's ability to fight cancer cells, offering hope for those with prostate cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Sebastien Hotte

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

Eric W Winquist

Principal Investigator

London Regional Cancer Program, London ON Canada

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to castration and has progressed despite treatment. They must have tried treatments like abiraterone or enzalutamide, can't have had certain immune therapies before, and need functioning major organs. No brain metastases or serious autoimmune diseases in the last 3 years, except for some exceptions like stable thyroid conditions.

Inclusion Criteria

I am a man and will use birth control if my partner can have children.

Patients must have at least one measurable lesion as defined by RECIST 1.1

My testosterone levels are below 50 ng/dL due to treatment.

Exclusion Criteria

Patients with hypersensitivity to durvalumab or tremelimumab

I have not received a live vaccine in the last 30 days.

Patients with active or prior documented autoimmune or inflammatory disorders within the past 3 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab alone or in combination with Tremelimumab. Durvalumab is administered intravenously for 60 minutes on day 1 every 4 weeks. Tremelimumab is administered intravenously for 60 minutes on day 1, cycles 1-4.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Tremelimumab

Trial Overview The trial is testing Durvalumab alone versus its combination with Tremelimumab on metastatic castration-resistant prostate cancer. It aims to understand their effects on this cancer type and monitor any side effects from these drugs when used separately or together.

How Is the Trial Designed?

Group I: Arm B - Durvalumab alone Experimental Treatment 1 Intervention

Durvalumab-IV for 60 minutes day 1 every 4 weeks

Group II: Arm A - Durvalumab plus Tremelimumab Experimental Treatment 2 Interventions

Durvalumab-IV for 60 minutes day 1 every 4 weeks Tremelimumab-IV every 60 minutes day 1, cycles 1-4

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10034400/

Randomized phase II trial in prostate cancer with hormone ... POSTCARD is a randomized multicentric phase II trial. Including patients with prostate cancer and hormone-sensitive oligometastatic relapse.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8536

A phase II study of durvalumab (MEDI4736) immediately ... Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03795207

Study Details | NCT03795207 | Prostate Cancer With ... The hypothesize is that Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this randomized 2:1 phase II trial of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/46/NCT04003246/Prot_SAP_000.pdf

STU 2019-1082 Phase II Concurrent Durvalumab ( ... Outcomes in the durvalumab arm were significantly better, regardless of tumor PDL1 status.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03528694

Study Details | NCT03528694 | Assessment of Efficacy and ... The safety and tolerability profile of Durvalumab + BCG combination therapies compared to SoC using vital signs, laboratory data, electrocardiograms (ECGs), and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405630823000381

Randomized phase II trial in prostate cancer with hormone ... In a comparable study, patients with a single metastasis had 5-year cancer-specific survival of 90% compared with only 32% in patients with more than one ...

8. researchgate.net researchgate.net/publication/327480949_Safety_and_clinical_activity_of_durvalumab_MEDI4736_an_anti-PD-L1_antibody_in_treatment-naive_patients_with_advanced_non-small-cell_lung_cancer

Safety and clinical activity of durvalumab (MEDI4736), an ... Encouraging ORR of 23% irrespective of PD-L1 status was observed in patients treated with durvalumab 20 mg/kg and tremelimumab 1 mg/kg (24) .