AZD0754 for Prostate Cancer
(APOLLO Trial)
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: AstraZeneca
Must be taking: Androgen deprivation therapy
Must not be taking: Anticoagulants, Corticosteroids
Disqualifiers: Brain metastases, Autoimmune disorders, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the safety, tolerability, and antitumour activity of AZD0754 CAR T-cell therapy in participants with metastatic prostate cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you must continue any medical castration therapy if you are on it, and you cannot receive certain full-dose anticoagulants or recent anticancer therapies close to the study start. It's best to discuss your specific medications with the study team.
What safety data exists for AZD0754 in humans?
There is no specific safety data available for AZD0754, but a similar compound, AZD3514, has been evaluated in clinical trials for prostate cancer, showing it is generally safe in humans.
12345How does the drug AZD0754 differ from other prostate cancer treatments?
AZD0754 is unique because it likely targets androgen receptor (AR) signaling, similar to AZD3514, which inhibits both androgen-dependent and independent AR signaling. This approach is particularly important for treating castration-resistant prostate cancer, where traditional hormone therapies fail.
13678Eligibility Criteria
This trial is for individuals with metastatic prostate cancer. Participants should meet specific health criteria to be eligible, but the exact inclusion and exclusion details are not provided.Inclusion Criteria
My prostate cancer is growing despite hormone therapy.
My prostate cancer has spread, and it's not small cell or neuroendocrine type.
I have had treatments like abiraterone or taxane for prostate cancer, or I cannot or will not take taxane.
+8 more
Exclusion Criteria
Participants with prior solid organ transplantation
I had cancer before, but it was treated over 2 years ago and is not likely to come back.
I have brain metastases.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive AZD0754 CAR T-cell therapy to evaluate safety, tolerability, and antitumour activity
Variable, up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The study is testing AZD0754 CAR T-cell therapy's safety, how well people can handle it, and its effectiveness in treating metastatic prostate cancer.
1Treatment groups
Experimental Treatment
Group I: AZD0754Experimental Treatment1 Intervention
AZD0754 monotherapy for treatment of participants with metastatic prostate cancer.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteHackensack, NJ
Research SiteTampa, FL
Research SiteHouston, TX
Research SiteWestwood, KS
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. [2021]Continued androgen receptor (AR) expression and signaling is a key driver in castration-resistant prostate cancer (CRPC) after classical androgen ablation therapies have failed, and therefore remains a target for the treatment of progressive disease. Here, we describe the biological characterization of AZD3514, an orally bioavailable drug that inhibits androgen-dependent and -independent AR signaling. AZD3514 modulates AR signaling through two distinct mechanisms, an inhibition of ligand-driven nuclear translocation of AR and a downregulation of receptor levels, both of which were observed in vitro and in vivo. AZD3514 inhibited testosterone-driven seminal vesicle development in juvenile male rats and the growth of androgen-dependent Dunning R3327H prostate tumors in adult rats. Furthermore, this class of compound showed antitumor activity in the HID28 mouse model of CRPC in vivo. AZD3514 is currently in phase I clinical evaluation.
Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up. [2014]Trial 24, one of three ongoing trials in the Early Prostate Cancer programme, is evaluating the efficacy and tolerability of bicalutamide (Casodex) 150 mg following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with early, non-metastatic prostate cancer. At 7 years' median follow-up, addition of bicalutamide significantly improved objective progression-free survival (PFS) for patients with locally advanced disease, reducing the risk of progression by 34% versus standard care alone (hazard ratio 0.66; 95% confidence interval 0.55, 0.79; P
Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells. [2021]AZD3514 inhibits and down regulates the androgen receptor (AR) and has undergone clinical trials in prostate cancer. To provide proof-of-mechanism (POM) in patients, an immunohistochemistry (IHC) method for determination of AR in circulating tumour cells (CTC) was developed and validated.
Efficacy of combined androgen blockade with zoledronic acid treatment in prostate cancer with bone metastasis: the ZABTON-PC (zoledronic acid/androgen blockade trial on prostate cancer) study. [2022]Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in castration-resistant prostate cancer (CRPC) with bone metastasis and improves quality of life. It remains unclear when clinicians should initiate ZA treatment.
Docetaxel with or without zoledronic acid for castration-resistant prostate cancer. [2021]The aim of this study was to evaluate the efficacy and safety of zoledronic acid (ZA) in the combination of docetaxel-based chemotherapy for castration-resistant prostate cancer with bone metastases.
Multidrug resistance protein 4 (MRP4) expression in prostate cancer is associated with androgen signaling and decreases with tumor progression. [2021]Multidrug resistance protein 4 (MRP4) is a transmembrane transport protein found in many cell types and is involved in substrate-specific transport of endogenous and exogenous substrates. Recently, it has shown to be expressed in prostate cancer cell lines and to be among the most commonly upregulated transcripts in prostate cancer, although a comprehensive expression analysis is lacking so far. We aimed to investigate its expression by immunohistochemistry in a larger cohort of neoplastic and nonneoplastic prostate tissues (n = 441) and to correlate its expression with clinicopathological parameters including PSA-free survival times and molecular correlates of androgen signaling (androgen receptor (AR), prostate-specific antigen (PSA), and forkhead box A (FoxA)). MRP4 is widely expressed in benign and neoplastic prostate epithelia, but its expression gradually decreases during tumor progression towards castrate-resistant disease. Concordantly, it correlated with conventional prognosticators of disease progression and-within the group of androgen-dependent tumors-with AR and FoxA expression. Moreover, lower levels of MRP4 expression were associated with shorter PSA relapse-free survival times in the androgen-dependent group. In benign tissues, we found zone-dependent differences of MRP4 expression, with the highest levels in the peripheral and central zones. Although MRP4 is known to be regulated in prostate cancer, this study is the first to demonstrate a gradual downregulation of MRP4 protein during malignant tumor progression and a prognostic value of this loss of expression.
AR-regulated ZIC5 contributes to the aggressiveness of prostate cancer. [2022]The mechanisms by which prostate cancer (PCa) progresses to the aggressive castration-resistant stage remain uncertain. Zinc finger of the cerebellum 5 (ZIC5), a transcription factor belonging to the ZIC family, is involved in the pathology of various cancers. However, the potential effect of ZIC5 on PCa malignant progression has not been fully defined. Here, we show that ZIC5 is upregulated in PCa, particularly in metastatic lesions, in positive association with poor prognosis. Genetic inhibition of ZIC5 in PCa cells obviously attenuated invasion and metastasis and blunted the oncogenic properties of colony formation. Mechanistically, ZIC5 functioned as a transcription factor to promote TWIST1-mediated EMT progression or as a cofactor to strengthen the β-catenin-TCF4 association and stimulate Wnt/β-catenin signaling. Importantly, ZIC5 and the androgen receptor (AR) form a positive feed-forward loop to mutually stimulate each other's expression. AR, in cooperation with its steroid receptor coactivator 3 (SRC-3), increased ZIC5 expression through binding to the miR-27b-3p promoter and repressing miR-27b-3p transcription. In turn, ZIC5 potentiated AR, AR-V7, and AR targets' expression. Besides, ZIC5 inhibition reduced AR and AR-V7 protein expression and enhanced the sensitivity of PCa to enzalutamide (Enz) treatment, both in vitro and in vivo. These findings indicate that the reciprocal activation between AR and ZIC5 promotes metastasis and Enz resistance of PCa and suggest the therapeutic value of cotargeting ZIC5 and AR for the treatment of advanced PCa.
Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis. [2020]Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP).