STM-416 for Bladder Cancer

Recruiting at9 trial locations

Overseen by Seth P. Lerner

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: SURGE Therapeutics

Must not be taking: Investigational agents

Disqualifiers: CIS, MIBC, Uncontrolled illness, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests STM-416, a new treatment, in bladder cancer patients whose disease has returned after standard treatments. The treatment is given to see if it is safe and effective.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot participate if you are receiving any other investigational agents.

What data supports the effectiveness of the treatment STM-416 for bladder cancer?

The research on hydrogel-based delivery systems, like the one used in STM-416, shows promise in improving treatment effectiveness by increasing retention time and penetration in the bladder wall, as seen in similar gel systems for bladder cancer. Additionally, the use of resiquimod, an immune response modifier, in combination with other treatments has shown potential in enhancing therapeutic effects. ^{1 2 3 4 5}

What safety data exists for STM-416 or similar treatments in humans?

TMX-101, a liquid form of imiquimod similar to STM-416, has been shown to be safe in early clinical trials for bladder cancer. Additionally, a hydrogel form of resiquimod, related to STM-416, is being tested for safety in cancer patients, aiming to reduce side effects by keeping the drug localized. ^{6 7 8 9 10}

How is the drug STM-416 unique for treating bladder cancer?

STM-416, also known as SURGERx with resiquimod, is unique because it uses a hydrogel-based formulation of resiquimod, which is a toll-like receptor 7 (TLR-7) agonist. This formulation allows for targeted delivery directly to the bladder, potentially enhancing its effectiveness and safety compared to traditional systemic treatments. ^{4 6 10 11 12}

Research Team

Seth P. Lerner

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with high-risk recurrent bladder cancer who are undergoing TURBT. They must have a certain level of physical fitness (ECOG 0-2) and adequate organ/marrow function. Excluded are those with invasive or carcinoma in situ bladder cancers, on other trials, allergic to similar drugs as STM-416, women who can become pregnant (only in early phases), and anyone with serious infections or unstable health conditions.

Inclusion Criteria

You are at a high risk of the condition coming back.

My blood counts and liver/kidney functions are within safe ranges.

I have had high-grade bladder cancer, treated but now recurred, and am undergoing a specific bladder tumor surgery without chemotherapy.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I may have a urinary tract infection, but it is not severe.

I am allergic to ingredients similar to those in STM-416.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Open-label, single-treatment, dose-escalation study to evaluate the safety and tolerability of STM-416 administered intraoperatively

21 days

Intraoperative administration, followed by monitoring

Treatment Phase 2a

Randomized, single-blind, single-treatment, dose-expansion study with two arms: TURBT + STM-416 Dose 1 followed by SOC versus TURBT + STM-416 Dose 2 followed by SOC

Up to 24 months

Regular follow-ups including cystoscopy and urine cytology

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days

Treatment Details

Interventions

• STM-416 (Other)

Trial Overview The study tests STM-416's safety and tolerability in patients with bladder cancer. It's the first time this drug is being tried on humans (Phase 1/2a). The trial involves increasing doses to find out what amount is safe and how well it works when given during TURBT surgery for recurring non-muscle-invasive bladder cancer.

Participant Groups

Group I: STM-416 Experimental Treatment 1 Intervention

STM-416

Who Is Running the Clinical Trial?

SURGE Therapeutics

Lead Sponsor

Trials

3

Recruited

120+

Findings from Research

Endovesical chemotherapy after bladder tumor removal is crucial for reducing recurrence and progression rates in non-muscle invasive bladder cancer, especially as traditional treatments like BCG and MMC have limitations.

Recent advancements in drug options and administration techniques, including hyperthermia, show promising preliminary results, suggesting a positive outlook for urologists treating bladder cancer with new and effective alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New endovesical chemotherapy and means of administration: EMD, HIVEC, Synergo, Unithermia.] Guerrero-Ramos, F., Rodríguez-Antolín, A.[2020]

The study developed a new treatment for bladder cancer using folate-modified liposomes (R-FL) encapsulated in a hydrogel, which showed enhanced cellular uptake in bladder cancer cells and improved drug retention in the bladder.

In an orthotopic bladder cancer mouse model, the R-FL/P407 formulation demonstrated significantly greater tumor growth inhibition compared to conventional liposomes, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel. Yoon, HY., Chang, IH., Goo, YT., et al.[2022]

The smart gel system developed for single instillation (SI) significantly enhances the treatment of non-muscle-invasive bladder cancer by effectively preventing re-implantation of tumor cells and ablating residual tumor lesions, using a combination of photothermal therapy and chemotherapy.

This gel system adheres selectively to tumor tissues, forming a protective layer that improves retention time and efficacy of the treatment, suggesting a promising new strategy for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A gel system for single instillation of non-muscle-invasive bladder Cancer: A "divide-and-rule" strategy. Guo, P., Shang, W., Peng, L., et al.[2022]

In a multicenter trial involving 193 primary and 121 recurrent cases of superficial bladder cancer, the combination of 20 mg Adriamycin and 200 mg cytosine arabinoside showed a significantly higher 12-month nonrecurrence rate (86.2%) compared to the control group (68.4%), indicating its efficacy in preventing recurrence after surgery.

For recurrent cases, no significant differences in nonrecurrence rates were observed with various oral drugs, suggesting that while intravesical treatment with ADM+CA is beneficial for primary cases, further research is needed to improve outcomes for recurrent bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic chemotherapy for primary and recurrent superficial bladder cancer: preliminary results. The Hokkaido University Bladder Cancer Collaborating Group. Togashi, M., Shinohara, N., Toyota, K., et al.[2019]

TMX-101, a novel formulation of imiquimod for intravesical delivery, was found to be safe and well tolerated in a phase 2 trial involving 12 patients with non-muscle-invasive bladder cancer, with only mild adverse effects reported.

The treatment showed potential clinical activity, as evidenced by two patients achieving negative biopsy and cytology results at 6 weeks post-treatment, along with significant increases in urinary cytokines, indicating an immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer. Donin, NM., Chamie, K., Lenis, AT., et al.[2022]

In a study of 20 patients with nonmuscle invasive bladder cancer, a single intravesical instillation of apaziquone after tumor resection was well tolerated, with 65% reporting mild adverse events, primarily dysuria and hematuria.

Pharmacokinetic analyses showed that apaziquone and its active metabolite EO5a were not detected in the bloodstream, indicating a favorable safety profile and minimal systemic exposure, which supports further investigation of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer. Hendricksen, K., Gleason, D., Young, JM., et al.[2014]

In a phase 1 trial involving 7 patients with low-grade non-muscle-invasive bladder cancer (NMIBC), TMX-101 did not achieve a complete response in any patient, indicating that the effective biologic dose could not be established.

Despite the lack of complete responses, TMX-101 was found to be safe, with all reported adverse events being of grade 2 severity or less, and no significant changes in laboratory parameters or vital signs during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer. Arends, TJ., Lammers, RJ., Falke, J., et al.[2022]

The TransCon Hydrogel technology enables sustained release of anti-cancer drugs directly into tumors, allowing for high local drug concentrations while minimizing systemic exposure, which could enhance efficacy and reduce side effects.

This method has been shown to effectively release drugs like resiquimod and axitinib over several weeks, and a hydrogel prodrug of resiquimod is currently being tested in clinical trials for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs. Lessmann, T., Jones, SA., Voigt, T., et al.[2023]

TMX-101, a liquid formulation of imiquimod, was found to be safe for treating nonmuscle invasive bladder cancer in a phase 1 study involving 16 patients, with no serious adverse events reported during 88 instillations.

Most adverse events were mild or moderate, primarily affecting the genitourinary tract, and there was low systemic uptake of the drug, indicating a favorable safety profile compared to previous studies of imiquimod.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer. Falke, J., Lammers, RJ., Arentsen, HC., et al.[2022]

The study demonstrates that combining antisense oligonucleotides targeting heat shock protein-27 (Hsp27) with the chemotherapy drug HTI-286 significantly enhances the drug's effectiveness against high-risk bladder cancer, as shown in both cell line studies and an orthotopic murine model.

This combination therapy works by inactivating the Akt signaling pathway and down-regulating Bcl-2, leading to increased chemosensitivity, and importantly, it does so without causing toxic side effects, making it a promising new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. Matsui, Y., Hadaschik, BA., Fazli, L., et al.[2020]

In a study of 127 non-muscle invasive bladder cancer patients, the combination of pirarubicin and hyaluronic acid significantly improved relief from pelvic pain and urinary symptoms compared to pirarubicin alone, with notable improvements observed within the first month (P = 0.04).

While the combination treatment did not show a significant difference in preventing cancer recurrence, it was deemed safe, with no adverse events related to hyaluronic acid, indicating it could be a beneficial addition to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle invasive bladder cancer after transurethral resection: a prospective, randomized study. Huang, W., Wang, F., Wu, C., et al.[2018]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[New endovesical chemotherapy and means of administration: EMD, HIVEC, Synergo, Unithermia.] [2020]

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

Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A gel system for single instillation of non-muscle-invasive bladder Cancer: A "divide-and-rule" strategy. [2022]

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

Prophylactic chemotherapy for primary and recurrent superficial bladder cancer: preliminary results. The Hokkaido University Bladder Cancer Collaborating Group. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[Long-term anti-cancer implants inhibiting the activity of tumor growth in animal models]. [2014]

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

A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer. [2022]

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

Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer. [2014]

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

Pharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer. [2022]

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

Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs. [2023]

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

Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer. [2022]

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

Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle invasive bladder cancer after transurethral resection: a prospective, randomized study. [2018]