AGN-CognI.Q for Prostate Cancer

Overseen By Xin Liu, MD, Ph.D

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Milton S. Hershey Medical Center

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a herbal supplement from Angelica gigas Nakai root in prostate cancer patients with recurrent disease. The goal is to see how the body processes and reacts to the supplement, potentially delaying or avoiding further hormonal therapy. Angelica gigas Nakai root has been used in traditional medicine in Korea and has shown various bioactivities, including anticancer properties.

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.

What data supports the idea that AGN-CognI.Q for Prostate Cancer is an effective treatment?

The available research does not provide specific data on AGN-CognI.Q for Prostate Cancer. Instead, it focuses on other treatments like apalutamide, which has been shown to improve survival and quality of life in prostate cancer patients. Without direct evidence for AGN-CognI.Q, we can't conclude its effectiveness for prostate cancer based on the provided information. ^{1 2 3 4 5}

What safety data exists for AGN-CognI.Q in prostate cancer treatment?

The provided research does not contain specific safety data for AGN-CognI.Q, Cogni-Q, or PQQ + CoQ10 in the treatment of prostate cancer. The studies focus on androgen deprivation therapy and its cognitive effects, but do not mention AGN-CognI.Q or related compounds. ^{2 6 7 8 9}

Is the drug AGN-CognI.Q a promising treatment for prostate cancer?

The information provided does not mention AGN-CognI.Q or its effects on prostate cancer, so we cannot determine if it is a promising treatment based on the given research articles. ^{10 11 12 13 14}

Research Team

Monika Joshi

Principal Investigator

Penn State Cancer Institute

Eligibility Criteria

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.

Treatment Details

Interventions

• AGN-CognI.Q (Other)

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

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

Estradiol and cognition during androgen deprivation in men with prostate carcinoma. [2013]

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

Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. [2013]

4. United States 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. [2022]

5. England 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. [2023]

6. United States 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. [2021]

7. Egypt pubmed.ncbi.nlm.nih.gov

Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation. [2023]

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

Androgen Deprivation Therapy and Future Alzheimer's Disease Risk. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy and cognitive decline-associations with brain connectomes, endocrine status, and risk genotypes. [2022]

10. United States 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. [2022]

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

Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). [2017]

12. England 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. [2023]

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

Identification of targets for prostate cancer immunotherapy. [2021]

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

Transcriptional mediators of treatment resistance in lethal prostate cancer. [2023]