AGN-CognI.Q for Prostate Cancer

Overseen By Xin Liu, MD, Ph.D

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Chemotherapy, Immunotherapy, Warfarin, others

Disqualifiers: Metastatic cancer, Heart failure, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called AGN-CognI.Q (also known as Cogni-Q or PQQ + CoQ10) for prostate cancer, focusing on its safety and behavior in the body. Researchers aim to determine how different doses affect prostate cancer patients. The trial seeks men who have had prostate cancer, are not on hormone therapy, and have a good performance status, meaning they can perform daily activities without significant limitations. This opportunity allows those who meet these criteria and are not currently undergoing specific cancer treatments to contribute to advancing cancer care. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop taking my current medications for this trial?

You must stop taking strong inhibitors or inducers of CYP3A4 and CYP2C19 two weeks before and during the study. Also, discontinue any herbal supplements containing AGN extract, including CognI.Q, Decursinol-50, Ache Action, Fast-Acting Joint Formula, and EstroG-100/Profemin, four weeks before starting the study. If you are on androgen deprivation therapy or taking Warfarin/Coumadin, you cannot participate in the trial.

Will I have to stop taking my current medications?

You will need to stop taking any strong inhibitors or inducers of CYP3A4 and CYP2C19 enzymes two weeks before and during the study. Additionally, if you are taking any herbal supplements containing AGN extract, you must stop these four weeks before starting the study drug. If you are on Warfarin/Coumadin, you cannot participate in the trial.

Is there any evidence suggesting that AGN-CognI.Q is likely to be safe for humans?

Research has shown that specific safety information for AGN-CognI.Q in treating prostate cancer is limited. Existing studies lack detailed insights into side effects or patient tolerance. However, AGN-CognI.Q contains ingredients like Coenzyme Q10 (CoQ10) and PQQ, which are common in supplements. CoQ10 is known for potential health benefits and is generally considered safe, but strong evidence of its direct effect on prostate cancer treatment is lacking. As this trial is in its early stages, it primarily focuses on assessing the treatment's safety and how the body processes it. The study is just beginning to collect safety data in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AGN-CognI.Q for prostate cancer because it offers a novel approach by focusing on a unique dosage regimen. Unlike traditional treatments like hormone therapy, chemotherapy, or surgery, AGN-CognI.Q is administered through oral capsules, potentially increasing convenience and compliance for patients. This treatment explores different dosage levels (800 mg, 1,200 mg, and 1,600 mg) with a fasting protocol, which may optimize absorption and effectiveness. By offering a potentially less invasive option, AGN-CognI.Q could present a new avenue for managing prostate cancer with fewer side effects.

What evidence suggests that AGN-CognI.Q might be an effective treatment for prostate cancer?

Research suggests that AGN-CognI.Q, the treatment under study in this trial, might aid in prostate cancer treatment due to its inclusion of Coenzyme Q10 (CoQ10) and Pyrroloquinoline Quinone (PQQ). Some studies have indicated that moderate blood levels of CoQ10 might reduce prostate cancer risk. Additionally, CoQ10 and PQQ together may exhibit anti-cancer effects by boosting energy production in cells and protecting them from damage. However, evidence in humans remains limited, and further research is necessary to confirm these effects in prostate cancer patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Monika Joshi

Principal Investigator

Penn State Cancer Institute

Are You a Good Fit for This Trial?

Men over 40 with prostate cancer, not on androgen deprivation therapy or having metastatic cancer. They must have stopped certain herbal supplements and strong CYP3A4/CYPC19 inhibitors/inducers for specific periods before the trial. Participants need normal liver/kidney function, acceptable blood counts, a life expectancy over 12 months, and agree to use effective contraception.

Inclusion Criteria

I have low-risk prostate cancer and have not started or chosen to forgo treatment.

I am not currently on hormone therapy for cancer.

I have had prostate cancer before, but it wasn't neuroendocrine or small cell type.

Exclusion Criteria

I am currently on hormone therapy for my cancer.

I do not have severe heart problems or recent heart attacks.

I am currently on chemotherapy, oral TKI, or immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGN-CognI.Q at various dose levels to assess acute dose safety and pharmacokinetics/pharmacodynamics

5-6 weeks

Weekly visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AGN-CognI.Q

Trial Overview The trial is testing AGN-CognI.Q's safety at different doses and how it affects the body (pharmacokinetics/pharmacodynamics) in men with prostate cancer. It aims to understand how the drug behaves after an acute dose and its potential effects on this patient group.

How Is the Trial Designed?

Group I: AGN-CognI.Q Experimental Treatment 1 Intervention

Dose level +1 (800 mg, 4 CognI.Q capsules, Fast at least 2 h before dose and 1 h after) Dose level +2 (1,200 mg, 6 CognI.Q capsules, Fast at least 2 h before dose and 1 h after) Dose level +3 (1,600 mg, 8 CognI.Q capsules, Fast at least 2 h before dose and 1 h after)

AGN-CognI.Q is already approved in Canada for the following indications:

Approved in Canada as Cogni-Q for:

• Cognitive health
• Mitochondrial function
• Antioxidant support

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

This clinical trial aims to evaluate the efficacy and safety of apalutamide in 110 patients with metastatic castration-resistant prostate cancer, focusing on the primary outcome of prostate-specific antigen (PSA) response rate, defined as a ≥50% decline from baseline at 12 weeks.

The study will also assess various secondary outcomes, including time to PSA progression and overall survival, while monitoring for any grade 3 or 4 adverse events, ensuring a comprehensive evaluation of both effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer (GENESIS): protocol for a multicentre, open-label, single-arm clinical trial. Miyake, H., Kakei, Y., Nakano, Y., et al.[2023]

A study involving 16,888 prostate cancer patients found that those receiving androgen deprivation therapy (ADT) had a significantly higher risk of developing Alzheimer's disease, with a hazard ratio of 1.88 in propensity score-matched analysis.

The risk of Alzheimer's disease increased with the duration of ADT use, indicating that longer treatment may further elevate this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen Deprivation Therapy and Future Alzheimer's Disease Risk. Nead, KT., Gaskin, G., Chester, C., et al.[2022]

The study analyzed the immune microenvironment of 19 prostate cancer samples, identifying CD276, PVR, and NECTIN2 as highly expressed targets that could be important for developing new immunotherapies.

Differential expression of genes related to immune response and epithelial-to-mesenchymal transition was observed between castration-resistant and castration-sensitive prostate cancer, highlighting the potential of targeting the PVR/NECTIN2/CD226/TIGIT pathway for checkpoint inhibition in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of targets for prostate cancer immunotherapy. Papanicolau-Sengos, A., Yang, Y., Pabla, S., et al.[2021]

Tasquinimod has shown effectiveness in inhibiting the formation of metastases in castration-resistant prostate cancer, as demonstrated in both orthotopic and intratibial xenograft models.

The treatment appears to work by inducing molecular changes, such as upregulating thrombospondin 1 and downregulating hypoxia-driven genes, which contribute to its anti-angiogenic and anti-metastatic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). Jennbacken, K., Welén, K., Olsson, A., et al.[2017]

In the SPARTAN trial involving 1207 men with high-risk non-metastatic castration-resistant prostate cancer, apalutamide significantly improved metastasis-free survival compared to placebo, indicating its efficacy in delaying cancer progression.

Patients receiving apalutamide maintained their health-related quality of life (HRQOL) throughout treatment, while those on placebo experienced a deterioration in HRQOL, suggesting that apalutamide not only extends survival but also preserves the quality of life during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Saad, F., Cella, D., Basch, E., et al.[2021]

Single-cell transcriptome analysis of 14 patients with metastatic castration-resistant prostate cancer revealed that cancer cells often coexpress multiple androgen receptor isoforms, including truncated forms that may contribute to resistance against androgen-targeting therapies.

Resistance to the drug enzalutamide was linked to specific cellular changes, such as epithelial-mesenchymal transition and activation of transforming growth factor-β signaling, suggesting potential new targets for therapy that could enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional mediators of treatment resistance in lethal prostate cancer. He, MX., Cuoco, MS., Crowdis, J., et al.[2023]

In a study of 11 prostate cancer patients on androgen deprivation therapy (ADT), no significant differences in neuroinflammation were found between those reporting cognitive impairment and those with normal cognition, suggesting that neuroinflammation may not be the primary cause of cognitive issues related to ADT.

Despite the lack of differences in neuroinflammation, a strong correlation was observed between neuroinflammation markers and brain activation in areas associated with memory, indicating that ADT may influence cognitive function through mechanisms that involve compensatory brain activity rather than direct neuroinflammatory damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation. Saleem, A., Shah, SIA., Mangar, SA., et al.[2023]

Prostate cancer patients undergoing androgen deprivation therapy (ADT) showed significant cognitive decline in 13 out of 15 cognitive outcomes compared to healthy controls, particularly in verbal memory and visuospatial learning, indicating a potential cognitive risk associated with ADT.

The study found that while testosterone levels decreased in patients, they did not predict cognitive decline, and specific genetic factors (COMT Met homozygotes) were linked to greater reductions in visuospatial memory, suggesting a complex interplay of genetics and treatment effects on cognition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy and cognitive decline-associations with brain connectomes, endocrine status, and risk genotypes. Buskbjerg, CR., Amidi, A., Buus, S., et al.[2022]

In a phase II trial involving 201 men with metastatic castration-resistant prostate cancer, tasquinimod significantly improved overall survival (OS) to 33.4 months compared to 30.4 months for placebo, particularly benefiting those with bone metastases.

Tasquinimod also demonstrated a favorable safety profile, with mostly mild side effects that improved over time, and showed potential biomarker correlates indicating its efficacy, such as lower levels of thrombospondin-1 predicting better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer. Armstrong, AJ., Häggman, M., Stadler, WM., et al.[2022]

EIQPN effectively blocks the activity of androgen receptor splice variants (AR-Vs) that contribute to drug resistance in advanced prostate cancer, by inducing degradation of AR proteins and inhibiting cancer cell proliferation.

In mouse models, EIQPN demonstrated the ability to significantly inhibit tumor growth of androgen-independent prostate cancer cells, suggesting its potential as a new treatment option for recurrent prostate cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new compound targets the AF-1 of androgen receptor and decreases its activity and protein levels in prostate cancer cells. Tran, TT., Song, CH., Kim, KJ., et al.[2021]

In a study of prostate cancer patients undergoing androgen deprivation therapy, significant cognitive changes were linked to declines in estradiol levels, particularly affecting visual memory and recognition speed at 6 months, and verbal fluency at 12 months.

The impact on cognitive performance varied depending on the extent of estradiol decline, suggesting that monitoring hormone levels could be important for managing cognitive side effects in patients receiving hormonal treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol and cognition during androgen deprivation in men with prostate carcinoma. Salminen, EK., Portin, RI., Koskinen, AI., et al.[2013]

In a study involving 82 men with non-localized prostate cancer, those receiving androgen-suppressing therapies (leuprorelin, goserelin, or cyproterone acetate) experienced increased sexual dysfunction and emotional distress over 12 months.

All treatment groups showed adverse effects on cognitive function compared to baseline, highlighting the need to consider these impacts when deciding on the timing of androgen suppression therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. Green, HJ., Pakenham, KI., Headley, BC., et al.[2013]

In the SPARTAN study involving 247 patients with nonmetastatic castration-resistant prostate cancer, the addition of apalutamide to androgen-deprivation therapy significantly improved metastasis-free survival and overall survival without increasing detectable androgen receptor or other genomic aberrations compared to ADT alone.

At the end of the study, higher levels of circulating-tumor DNA (ctDNA) and specific genetic aberrations (like AR, TP53, and BRCA2) were linked to worse outcomes, indicating that these biomarkers could help predict patient prognosis after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Biomarker Landscape in Patients with High-risk Nonmetastatic Castration-Resistant Prostate Cancer Treated with Apalutamide and Androgen-Deprivation Therapy as They Progress to Metastatic Disease. Smith, MR., Thomas, S., Gormley, M., et al.[2022]

In the TITAN study involving 1052 patients with metastatic castration-sensitive prostate cancer (mCSPC), apalutamide combined with androgen-deprivation therapy (ADT) significantly improved overall survival compared to ADT alone, particularly in patients with synchronous/high-volume disease.

Apalutamide demonstrated consistent benefits across various disease volumes and timing of metastasis presentation, with no significant differences in safety profiles, suggesting it is a safe and effective treatment option for mCSPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study. Merseburger, AS., Agarwal, N., Bhaumik, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05375539

Study Details | NCT05375539 | AGN-CognI.Q Acute Dose ... This study is to obtain acute dose safety and pharmacokinetics/pharmacodynamics (PK/PD) data in a dose-response trial in prostate cancer patients. Detailed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4439209/

Plasma Coenzyme Q10 levels and Prostate Cancer Risk The results suggest the possibility that moderate levels of circulating CoQ10 may be optimal for the reduction of prostate cancer risk.

3. cellmolbiol.org cellmolbiol.org/index.php/CMB/article/view/4741

Effects of Pyrroloquinoline Quinone (PQQ) and Coenzyme ... If the data we have obtained are evaluated in terms of anti-cancer effectiveness, the most effective use of CoQ10 can be defined as the use ...

4. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-8-2022-d5890

AGN-CognI.Q for Prostate Cancer · Info for Participants Prostate cancer patients undergoing androgen deprivation therapy (ADT) showed significant cognitive decline in 13 out of 15 cognitive outcomes compared to ...

5. trialx.com trialx.com/clinical-trials/listings/237846/agn-cogniq-acute-dose-safety-and-pharmacokinetics-dose-response-in-prostate-cancer-patients/

AGN-CognI.Q Acute Dose Safety and Pharmacokinetics ... This study is to obtain acute dose safety and pharmacokinetics/pharmacodynamics (PK/PD) data in a dose-response trial in prostate cancer ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/keydates/NCT05375539

AGN-CognI.Q Acute Dose Safety and Pharmacokinetics ... This study is to obtain acute dose safety and pharmacokinetics/pharmacodynamics (PK/PD) data in a dose-response trial in prostate cancer patients. Detailed ...

7. webmd.com webmd.com/vitamins-and-supplements/what-to-know-about-pqq-supplements

What Should You Know About PQQ Supplements? - WebMD Explore the potential benefits and risks of PQQ supplements and how they may support your overall health.