FX-909 for Bladder Cancer

Recruiting at13 trial locations

Overseen by Gopa Iyer, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Flare Therapeutics Inc.

Must not be taking: Insulin, Steroids, Anticancer, others

Disqualifiers: Pregnancy, HIV, Hepatitis, Diabetes, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new tablet called FX-909 for safety and proper dosage in patients with advanced solid tumors, especially advanced urothelial carcinoma. Doctors will closely monitor patients to understand how the drug works and its effects on the body and tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you need certain treatments, like high doses of steroids or other prohibited therapies during the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug FX-909 for bladder cancer?

The research on enfortumab vedotin, a targeted therapy for advanced urothelial carcinoma, shows improved survival and response rates compared to standard chemotherapy, suggesting potential effectiveness for similar treatments like FX-909. ^{1 2 3 4 5}

How is the drug FX-909 different from other bladder cancer treatments?

FX-909 is a novel treatment for bladder cancer, but specific details about its mechanism or administration are not provided in the available research. Existing treatments like vinflunine and combinations of chemotherapy drugs such as cisplatin and 5-fluorouracil have been used, but they often come with significant side effects and limited survival benefits. ^{2 3 6 7 8}

Research Team

Gopa Iyer, MD

Principal Investigator

Memorial Slone Kettering

Eligibility Criteria

This trial is for adults (18+) with advanced solid tumors, including urothelial carcinoma, that have worsened after standard treatments or when such treatments aren't suitable. Participants must be in relatively good health otherwise (ECOG status 0-2), able to consent, and have a tumor sample available. Pregnant or breastfeeding women, individuals with recent serious heart issues, uncontrolled infections like HIV/HCV, severe lung function impairment, certain gastrointestinal disorders, or those who've had recent chemotherapy are excluded.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and has not responded to or cannot be treated with standard therapies.

I can understand and am willing to sign a consent form.

Patients with or without measurable disease (as defined by RECIST version 1.1) will be eligible for enrollment

Exclusion Criteria

I have stable brain metastases with no symptoms after radiotherapy.

My side effects from previous treatments are mild or have returned to normal, except for hair loss, hearing loss, skin color changes, hormone issues treated with medication, and mild nerve pain.

I haven't had major surgery in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive FX-909 in a dose-escalation phase to determine the preliminary recommended phase 2 dose (RP2D)

28-day cycles

Multiple site visits for blood tests and sample collection

Monotherapy Expansion

Further evaluation of safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of FX-909 in patients with locally advanced and metastatic urothelial carcinoma

28-day cycles

Regular CT/MRI scans and site visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• FX-909 (Other)

Trial Overview The study tests the safety and appropriate dosage of FX-909 taken orally by patients with advanced cancers. It involves daily intake of FX-909 tablets while monitoring effects through regular site visits for blood tests and imaging scans like CT/MRI to assess how the body responds to the treatment over time.

Participant Groups

Group I: Expansion Expansion Experimental Treatment 1 Intervention

When a preliminary RP2D has been identified (this dose may be equal to or below the MTD) evaluate the antitumor activity in locally advanced (unresectable) and metastatic urothelial carcinoma.

Group II: Dose Escalation Experimental Treatment 1 Intervention

3+3 design, 5 dose levels,

Who Is Running the Clinical Trial?

Flare Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

80+

Findings from Research

In a study of 6007 urothelial cancer patients, those who received enfortumab vedotin after pembrolizumab had significantly longer overall survival compared to those treated with paclitaxel or docetaxel, indicating its effectiveness as a life-prolonging therapy.

Enfortumab vedotin was identified as an independent risk factor for improved overall survival, suggesting it may be a valuable treatment option for Japanese patients with advanced urothelial carcinoma following prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma. Kawahara, T., Hasizume, A., Uemura, K., et al.[2023]

The FAP combination chemotherapy demonstrated a high response rate in advanced urothelial cancer, with 65% of patients showing objective responses, including 18% achieving complete responses, based on a study of 34 patients.

The treatment had manageable toxicity, with significant hematologic toxicity (grade 3-4 neutropenia) occurring in 44% of patients, while non-hematologic side effects were minimal, indicating that FAP is a promising first-line option for this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Fluorouracil, interferon-alpha-2b and cisplatin (FAP) for advanced urothelial cancer. A phase II study. Hellenic Co-operative Oncology Group. Kosmidis, PA., Bacoyiannis, C., Fountzilas, G., et al.[2020]

In a study of 45 patients with high-risk bladder cancer, the combination of transurethral resection of the bladder tumor (TURB) with concurrent cisplatin, 5-fluorouracil (5-FU), and radiation therapy resulted in an impressive 87% complete response rate, with 64% of patients remaining tumor-free after treatment.

The treatment protocol demonstrated acceptable safety, with only 10% experiencing severe hematologic toxicity and a 5-year survival rate of 54% with preserved bladder, indicating its efficacy and potential as a viable option for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil. Rödel, C., Grabenbauer, GG., Kühn, R., et al.[2019]

In a study of 106 patients with advanced urothelial cancer, the addition of Factor AF2 to chemotherapy resulted in increased myelotoxicity and gastrointestinal side effects compared to chemotherapy alone, indicating a potential safety concern.

Despite the supportive effects of Factor AF2, there was no significant difference in tumor response, median survival (33 weeks), or time to progression (20 weeks) between patients receiving Factor AF2 and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study]. Krege, S., Hinke, A., Otto, T., et al.[2019]

Vinflunine, while authorized for second-line treatment of advanced urothelial carcinoma, only increased median overall survival by 2 months compared to palliative care alone, which is not statistically significant in primary analyses.

The drug has a similar adverse effect profile to other vinca alkaloids, including serious hematological disorders and cardiac issues, leading to an unfavorable risk-benefit balance for patients with bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinflunine. [2013]

A study of 248 patients who underwent radical cystectomy for bladder cancer showed a 5-year survival rate of 69%, indicating that this surgical approach can be effective for managing bladder cancer, especially for tumors confined to the bladder.

Key risk factors for bladder cancer-specific death included extravesical tumor growth, high tumor grade, and positive lymph-node status, highlighting the importance of these factors in predicting patient outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty-year experience of radical cystectomy for bladder cancer in a medium-volume centre. Boström, PJ., Mirtti, T., Kössi, J., et al.[2022]

Bladder cancer, often linked to environmental and lifestyle factors, shows promising outcomes with early intervention; 87% of early-stage patients can achieve 10-year survival after appropriate treatment, although many still require radical cystectomy.

Recent studies suggest that the gemcitabine and cisplatin regimen is as effective as traditional chemotherapy with less toxicity, making it the new standard for advanced bladder cancer treatment in ongoing phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder cancer. Patton, SE., Hall, MC., Ozen, H.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

5-Fluorouracil, interferon-alpha-2b and cisplatin (FAP) for advanced urothelial cancer. A phase II study. Hellenic Co-operative Oncology Group. [2020]

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

Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

[Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study]. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Early Warning Models to Predict the 90-Day Urinary Tract Infection Risk After Radical Cystectomy and Urinary Diversion for Patients With Bladder Cancer. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Vinflunine. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Twenty-year experience of radical cystectomy for bladder cancer in a medium-volume centre. [2022]

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

Bladder cancer. [2022]