CGC Therapy for Bladder Cancer

(CGC Trial)

Not currently recruiting at 1 trial location

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Guarionex J. Decastro

Must not be taking: Cytochrome P450 drugs

Disqualifiers: Pregnancy, Concurrent malignancy, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug combination—Cabazitaxel, Cisplatin, and Gemcitabine—for individuals with bladder cancer unresponsive to standard treatments like BCG. The trial explores different doses to determine which is most effective with the fewest side effects. Participants should have bladder cancer that has returned or persisted after BCG treatment and must not be eligible or willing to undergo bladder removal surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

Will I have to stop taking my current medications?

The trial requires a one-week period without taking certain medications that strongly affect liver enzymes (cytochrome P450 3A4/5). If you're on these medications, you'll need to stop them for a week before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of Cabazitaxel, Gemcitabine, and Cisplatin for treating bladder cancer is under careful study for safety. Previous studies have found that patients can tolerate this drug combination when administered directly into the bladder. One study with 18 patients found this drug mix to be safe when used in a specific order.

Gemcitabine and Cisplatin together have demonstrated similar success rates to other traditional treatments but with fewer side effects, suggesting they might be safer than older options. Earlier research on Cabazitaxel has also shown promise as a treatment, though it remains under study.

While these results are encouraging, they come from studies focused on safety and effectiveness. The current phase of this trial gathers more detailed safety information. The data collected will help determine how well patients can handle this combination of drugs for bladder cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they combine cabazitaxel, cisplatin, and gemcitabine in an innovative way. Unlike the standard intravenous administration, these drugs are delivered intravesically, directly into the bladder, which might enhance their effectiveness and reduce systemic side effects. The unique combination of these drugs, particularly the varied doses of cabazitaxel and cisplatin, allows for a tailored approach that targets cancer cells aggressively. This method could potentially improve outcomes for patients who have not responded to traditional therapies like BCG or standard chemotherapy.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that using Gemcitabine and Cabazitaxel together may help treat bladder cancer. In one study, 86% of patients showed no signs of cancer after three months. Another study found that 83% of patients were cancer-free after one year. In this trial, participants will receive different combinations of these drugs. Some will receive Gemcitabine and Cabazitaxel at varying doses, while others will also receive Cisplatin. Early results from studies involving Cisplatin showed that 94% of patients experienced some improvement, and 89% had no signs of cancer. These drugs appear to work well together due to their strong combined effect on cancer cells. ^{1 3 6 7 8}

Who Is on the Research Team?

Guarionex DeCastro, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with non-muscle invasive bladder cancer resistant to BCG therapy. They must be eligible for but not wanting or able to undergo radical cystectomy, have an ECOG status of 0 or 1, and agree to use effective contraception. Exclusions include severe drug allergies, recent participation in other trials, certain treatments within the last 6 weeks, concurrent cancers or chemotherapy, and inadequate organ function.

Inclusion Criteria

All patients of childbearing potential must be willing to consent to using effective contraception while on treatment and for 3 months after their participation in the study ends

All visible bladder cancer has been surgically removed and its stage confirmed.

My bladder cancer is confirmed and not spread into the muscle.

Exclusion Criteria

I have a history of bladder reflux or currently have a urinary stent.

You have had a very bad allergic reaction to drugs containing polysorbate 80 in the past.

My organ and bone marrow functions are not meeting certain health standards.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical administration of Cabazitaxel, Gemcitabine, and Cisplatin once a week for 6 weeks

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Cisplatin
• Gemcitabine

Trial Overview The study tests a new combination of drugs (Cabazitaxel, Gemcitabine, Cisplatin) given directly into the bladder for those whose bladder cancer hasn't responded to standard treatment. Up to 24 patients will join this phase I trial which aims to find out how safe the treatment is and what dose is best.

How Is the Trial Designed?

Group I: Gem, High Cab, and Low Cis Experimental Treatment 3 Interventions

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 66mg/100ml; 1 time a week for 6 weeks; 2 hours

Group II: Gem, High Cab, Mod Cis Experimental Treatment 3 Interventions

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 80mg/100ml; 1 time a week for 6 weeks; 2 hours

Group III: Gem, High Cab, High Cis Experimental Treatment 3 Interventions

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 100mg/100ml; 1 time a week for 6 weeks; 2 hours

Group IV: Gem and Low Cab Experimental Treatment 2 Interventions

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 2.5mg/100ml; 1 time a week for 6 weeks; 2 hours

Group V: Gem and High Cab Experimental Treatment 2 Interventions

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours

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

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

Guarionex J. Decastro

Lead Sponsor

Trials

1

Recruited

50+

James M. McKiernan

Lead Sponsor

Trials

1

Recruited

50+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

Cisplatin is a key treatment for bladder cancer, but managing its side effects, like nausea and acute kidney injury, is crucial to maintain treatment effectiveness and avoid dose reductions.

An effective strategy for preventing cisplatin-associated nausea and vomiting involves a four-drug prophylactic regimen, while intensive hydration is essential for preventing acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of cisplatin-associated toxicities in bladder cancer patients. Desilets, A., Adam, JP., Soulières, D.[2021]

In a phase II trial involving 22 patients with muscle-invasive bladder cancer, the combination of gemcitabine and cisplatin (GC) showed a 70% radiologic response rate, indicating its effectiveness as a neoadjuvant treatment before surgery.

The treatment was well-tolerated, with infrequent severe toxicities and no chemotherapy-related deaths, suggesting it is a safe option for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma. Herchenhorn, D., Dienstmann, R., Peixoto, FA., et al.[2022]

In a phase II study involving 27 patients with advanced transitional cell carcinoma, the sequential treatment of gemcitabine and carboplatin followed by paclitaxel resulted in an objective response rate of 40.7%, with one complete response and ten partial responses.

The treatment was generally safe, with hematologic toxicities being the most common, but the study concluded that while this sequential approach appears safer than triplet therapy, it did not significantly improve patient outcomes, indicating a need for further research with larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. Kattan, JG., Boutros, CY., Farhat, FS., et al.[2021]

Citations

1. targetedonc.com targetedonc.com/view/early-efficacy-shown-with-gemcitabine-cabazitaxel-pembrolizumab-in-nmiuc

Early Efficacy Shown With Gemcitabine/Cabazitaxel/ ... Findings showed that at 3 months, the time of the first evaluation, 86% patients and 89% of treated units had CR. At 6 months post-treatment ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32118506/

A Phase I Trial of Intravesical Cabazitaxel, Gemcitabine and ... At 1 year recurrence-free survival was 0.83 (range 0.57 to 0.94) and at 2 years estimated recurrence-free survival was 0.64 (0.32 to 0.84). Conclusions: In this ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02202772

Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC ... These drugs have shown some potential improvement for a small number of patients Given the synergy of systemic chemotherapy, it is believed that a multidrug ...

4. urologytimes.com urologytimes.com/view/activity-of-cabazitaxel-gemcitabine-plus-pembrolizumab-in-heavily-pretreated-urothelial-carcinoma

Activity of cabazitaxel/gemcitabine plus pembrolizumab in ... Sequential valrubicin and docetaxel therapy showed efficacy in recurrent high-risk NMIBC, with 45% of patients disease-free at two years. · High- ...

5. mdpi.com mdpi.com/2072-6694/16/14/2561

Sequential Endoluminal Gemcitabine and Cabazitaxel with ... The 2-year progression-free and cancer-specific survival was 70% (CI: 44–85%) and 96% (CI: 75–99%), respectively. In total, 22/26 (85%) patients ...

6. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-bladder-cancer/154907-esmo-2024-a-phase-ii-trial-of-intravesical-cabazitaxel-gemcitabine-and-cisplatin-for-the-treatment-of-non-muscle-invasive-bcg-unresponsive-urothelial-carcinoma-of-the-bladder.html

ESMO 2024: A Phase II Trial of Intravesical Cabazitaxel, ... In 2019, a phase I study of 18 patients demonstrated the safety of a novel, sequential intravesical combination regimen of cabazitaxel, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8464350/

A Phase I Trial of Intravesical Cabazitaxel, Gemcitabine ... Intravesical gemcitabine monotherapy has shown limited efficacy in this high risk group, with 1-year RFS of 28%. Sequential use of salvage gemcitabine and ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0014299922002850

Intravesical combination therapies for non-muscle invasive ... Results showed that the treatment success was 53–55% for up to two years, about quarter of patients needed to eventually receive radical ...