Tinengotinib + Standard Treatments for Prostate Cancer

Recruiting at 10 trial locations

Overseen By Samir Zaidi, MD,PhD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Abiraterone, Enzalutamide

Must not be taking: Multi-TKI therapies, Corticosteroids

Disqualifiers: Small cell carcinoma, Hypertension, Heart failure, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether tinengotinib in combination with abiraterone acetate and prednisone or enzalutamide is a safe treatment that causes few or mild side effects in people with metastatic castration-resistant prostate cancer (mCRPC).

Do I need to stop my current medications to join the trial?

You will need to continue taking your current medication of either abiraterone acetate or enzalutamide at the full standard dose to participate in the trial. The trial requires that you have been on one of these medications for at least 90 days before joining.

What data supports the effectiveness of the drug Tinengotinib + Standard Treatments for Prostate Cancer?

Research shows that abiraterone acetate, a component of the treatment, is effective in prolonging survival and delaying disease progression in patients with metastatic castration-resistant prostate cancer when used with prednisone. ^{1 2 3 4 5}

Is Tinengotinib + Standard Treatments for Prostate Cancer safe for humans?

Abiraterone acetate, used in combination with prednisone, has been studied for safety in treating prostate cancer. It is generally considered safe, but there is a risk of metabolic (related to metabolism) and cardiovascular (heart-related) side effects. ^{1 4 6 7 8}

What makes the drug Tinengotinib + Abiraterone Acetate unique for prostate cancer?

Tinengotinib combined with Abiraterone Acetate is unique because it combines a novel drug, Tinengotinib, with an established treatment, Abiraterone Acetate, which is known to prolong survival in prostate cancer patients. This combination may offer a new approach by potentially enhancing the effectiveness of standard treatments. ^{1 3 4 5 9}

Research Team

Wassim Abida, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals with metastatic castration-resistant prostate cancer. Participants should not have had previous treatments that failed and must be healthy enough to take the study medications.

Inclusion Criteria

I have measurable cancer or my PSA level is 2.0 ng/mL or higher.

I can take care of myself and am up and about more than 50% of my waking hours.

My cancer has worsened despite taking enzalutamide or abiraterone.

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last 14 days.

I don't have any stomach or intestine problems that affect medication absorption.

I have brain metastases that are causing symptoms or have not been treated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tinengotinib in combination with abiraterone acetate and prednisone or enzalutamide for 28-day cycles

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Abiraterone Acetate
• Prednisone
• Tinengotinib

Trial Overview The trial tests Tinengotinib combined with standard prostate cancer treatments (abiraterone acetate and prednisone or enzalutamide) to see if it's a safe option that only causes mild side effects.

Participant Groups

Group I: Tinengotinib with enzalutamide Experimental Treatment 2 Interventions

Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily will be administered unless dose de-escalation is required in Phse 1b. Participants will receive Tinengotinib in combination with enzalutamide 160 mg PO QD.

Group II: Tinengotinib with abiraterone acetate/prednisone Experimental Treatment 2 Interventions

Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily will be administered unless dose de-escalation is required in Phase 1b. Participants will receive tinengotinib with abiraterone acetate 1000 mg PO QD in combination with prednisone 5 mg PO once or twice daily (QD or BID)

Abiraterone Acetate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

TransThera Sciences

Collaborator

Trials

1

Recruited

50+

Findings from Research

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

In a study of 12 men with metastatic castrate-resistant prostate cancer (mCRPC) who were re-treated with abiraterone acetate (AA), only 46% of those who initially responded to AA showed a similar response upon re-treatment, indicating limited efficacy.

The median duration of response to AA re-treatment was short, with a median biochemical progression-free survival of just 2.3 months, suggesting that re-challenging with AA may not provide significant long-term benefits for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. Leibowitz-Amit, R., Alimohamed, N., Vera-Badillo, FE., et al.[2016]

In the IPATential150 trial involving 1097 patients with metastatic castration-resistant prostate cancer, adding ipatasertib to abiraterone and prednisone significantly improved radiographic progression-free survival for patients with PTEN-loss tumors.

While ipatasertib was associated with a higher rate of serious adverse events and treatment discontinuation compared to placebo, its overall safety profile was considered tolerable, suggesting that with proper management, the side effects could be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. Matsubara, N., de Bono, J., Sweeney, C., et al.[2023]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

In a study of 93 men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA), the median survival was significantly longer for chemotherapy-naive patients (36.4 months) compared to those previously treated with chemotherapy (13.4 months).

The safety profile of AA was consistent with previous clinical trials, showing low rates of adverse events like hypokalemia and hypertension, suggesting that less intensive monitoring may be appropriate for patients without these complications after 7.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone in metastatic castration-resistant prostate cancer: Efficacy and safety in unselected patients. Marret, G., Doucet, L., Hennequin, C., et al.[2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. [2019]

3. Sweden pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. [2017]

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

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. [2018]

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

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. [2016]

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

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022]

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

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]

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

Abiraterone in metastatic castration-resistant prostate cancer: Efficacy and safety in unselected patients. [2019]