CG0070 for Bladder Cancer

Overseen By Syed Hasan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: High-risk NMIBC, Muscle invasive cancer, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests CG0070, a special virus designed to target and kill cancer cells, to determine its safety for treating certain types of bladder cancer. It focuses on patients with intermediate-risk, non-muscle invasive bladder cancer, meaning the cancer hasn't spread to the bladder's muscle layer. Suitable candidates have a type of bladder cancer that recurs or is larger than 3 cm, but not high-risk types, and should have a small, removable cancer spot that doctors can track. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use certain anti-viral medications and must be able to pause anti-platelet or anti-coagulant therapy for procedures. If you're on high-dose corticosteroids or certain other treatments, you may need to stop them before joining the trial.

Is there any evidence suggesting that CG0070 is likely to be safe for humans?

Research has shown that CG0070, a virus used to target cancer cells, has undergone safety testing for bladder cancer treatment. Earlier studies found it to be very safe, with no reports of serious side effects. Most side effects were mild to moderate, such as minor discomfort or irritation. These findings suggest that patients generally tolerate CG0070 well. This information can help prospective participants understand what to expect if they join a trial for CG0070. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CG0070 for bladder cancer because it offers a unique approach to treatment. Unlike traditional options like chemotherapy or immunotherapy, CG0070 is an oncolytic adenovirus that targets cancer cells specifically. This means it replicates within and destroys cancer cells while sparing healthy ones. This targeted action not only aims to improve effectiveness but also potentially reduces side effects, making it a promising new avenue for bladder cancer treatment.

What evidence suggests that CG0070 might be an effective treatment for bladder cancer?

Research has shown that CG0070, a treatment using a virus to target cancer cells, yields promising results for bladder cancer. In an earlier study with high-risk patients, about 75.5% showed no detectable cancer after treatment. Impressively, 58% of these patients remained cancer-free for two years. Additionally, 97.3% did not experience cancer progression, and 84.5% avoided bladder removal surgery. These findings suggest that CG0070, which participants in this trial will receive, could effectively manage bladder cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Roger Li, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Inclusion Criteria

Willing to use barrier contraception during sexual activity for up to 6 weeks after each dose of CG0070

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

My bladder cancer is confirmed to be a specific type and stage.

Exclusion Criteria

My bladder cancer is at a low risk of getting worse.

I have not had any cancer treatment in the last 4 weeks.

I have not had a heart attack or stroke in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CG0070 treatment after transurethral resection

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• CG0070

Trial Overview

This trial is focused on assessing the safety of a treatment called CG0070 for patients with Intermediate-Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC).

How Is the Trial Designed?

Group I: CG0070 Experimental Treatment 1 Intervention

CG0070 is a conditionally replicating oncolytic adenovirus (serotype 5) designed to preferentially replicate in and kill cancer cells.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

A study analyzed the protein expression of various cancer targets in different subtypes of bladder cancer, revealing that a significant percentage of patients could be eligible for targeted therapies: 58.9% of small cell neuroendocrine carcinoma (SCC) patients, 33.5% of adenocarcinomas (AC) and urachal carcinomas (UrC) patients, and 79.3% of squamous-differentiated bladder cancers (Sq-BLCA) patients.

The research suggests that personalized treatment options based on biomarker status could improve therapeutic outcomes for patients with nonurothelial bladder cancer, as many could benefit from specific targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer. Wucherpfennig, S., Rose, M., Maurer, A., et al.[2021]

CG0070 is an oncolytic adenovirus that specifically targets and kills cancer cells lacking the retinoblastoma (Rb) protein, making it a promising treatment for certain types of bladder cancer.

The study outlines standardized protocols for administering CG0070 intravesically, providing guidance for its use in patients with bladder cancer that does not respond to traditional BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical Infusion of Oncolytic Virus CG0070 in the Treatment of Bladder Cancer. Grandi, P., Darilek, A., Moscu, A., et al.[2023]

In a phase I/IIa trial involving eight patients with invasive bladder cancer, the intrabladder administration of AdCD40L gene therapy was found to be safe, with only minor side effects like transient local pain and some urinary tract infections, but no adverse events linked to the therapy itself.

The treatment successfully induced immune activation, as evidenced by increased T cell infiltration and elevated levels of the effector marker IFN-gamma in bladder biopsies, while also reducing the presence of malignant cells, suggesting potential efficacy in treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial. Malmström, PU., Loskog, AS., Lindqvist, CA., et al.[2021]

In a study of 64 patients with high-risk superficial bladder cancer, bacillus Calmette-Guérin (BCG) treatment resulted in a significantly lower recurrence rate (28.1%) compared to gemcitabine (53.1%), indicating that BCG is more effective for this condition.

Gemcitabine was better tolerated than BCG, with fewer patients needing delayed treatment or withdrawal, suggesting it could be a suitable alternative for those who cannot tolerate BCG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. Porena, M., Del Zingaro, M., Lazzeri, M., et al.[2022]

Antibody-drug conjugates (ADCs) like enfortumab vedotin and sacituzumab govitecan have shown significant efficacy in treating advanced urothelial carcinoma, with enfortumab vedotin being effective alone or in combination with pembrolizumab, and both having received FDA approval.

Common side effects of these treatments include rash and neuropathy for enfortumab vedotin, and myelosuppression and diarrhea for sacituzumab govitecan, highlighting the importance of monitoring patient safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates for urothelial carcinoma. Thomas, J., Sun, M., Getz, T., et al.[2023]

Immune checkpoint inhibitors have emerged as a promising alternative to traditional platinum-based chemotherapy for advanced urothelial cancer, showing better toxicity profiles and efficacy, although most patients still do not respond to these treatments.

There is a critical need for new therapeutic options and biomarkers to predict treatment responses, as ongoing clinical trials are exploring various combinations of therapies, including novel agents like enfortumab vedotin and erdafitinib, which have received breakthrough designation from the FDA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conceptual Framework for Therapeutic Development Beyond Anti-PD-1/PD-L1 in Urothelial Cancer. Grivas, P., Drakaki, A., Friedlander, TW., et al.[2019]

Urothelial carcinoma remains a significant health challenge, with advanced cases having a median overall survival of nearly 1 year despite being sensitive to chemotherapy, highlighting the urgent need for new treatment options.

Emerging therapies, including new cytostatic agents and targeted therapies such as anti-EGFR and PI3K/mTOR inhibitors, are currently being evaluated in clinical trials, indicating a shift towards more innovative treatment strategies for this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for urothelial cancer. Serrano, C., Morales, R., Suárez, C., et al.[2012]

In a phase II trial involving 45 patients with high-grade non-muscle invasive bladder cancer (NMIBC) who were unresponsive to BCG treatment, intravesical CG0070 achieved a 47% complete response rate at 6 months, with a notable 58% response rate in patients with pure carcinoma in situ (CIS).

The treatment was generally well-tolerated, with common side effects including urinary bladder spasms and hematuria, but no severe (Grade IV/V) adverse events were reported, indicating a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Packiam, VT., Lamm, DL., Barocas, DA., et al.[2018]

Screening 17 bladder cancer cell lines in 3D culture using 652 investigational small molecules revealed that this method is more representative of in vivo drug responses compared to traditional 2D culture.

The study identified MEK inhibitors as a promising targeted therapy specifically for the basal subtype of bladder cancer, highlighting the potential of 3D drug screening to uncover effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEK is a promising target in the basal subtype of bladder cancer. Merrill, NM., Vandecan, NM., Day, KC., et al.[2020]

In a study of 480 patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), those who switched to chemotherapy after discontinuing bacillus Calmette-Guérin (BCG) treatment had a significantly better three-year recurrence-free survival (RFS) rate compared to those who did not receive any further treatment.

The chemotherapy replacement group had a higher total number of instillations (14.9) compared to the pure BCG group (10.5), and multivariate analysis showed that the pure BCG group had more than double the risk of recurrence, highlighting the potential efficacy of chemotherapy as a replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer. Lin, PT., Hung, WK., Chang, YH., et al.[2023]

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