CGC Therapy for Bladder Cancer

(CGC Trial)

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

51 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Cabazitaxel, Jevtana, Cisplatin, Platinol, Cisplatinum, platamin, neoplatin, cismaplat, cis-diamminedichloroplatinum(II), CDDP, Gemcitabine, Gemzar for bladder cancer?

Research shows that cisplatin-based chemotherapy improves survival in muscle-invasive bladder cancer, and gemcitabine combined with cisplatin has shown favorable results in terms of effectiveness and safety. Additionally, studies indicate that combinations including cabazitaxel, gemcitabine, and cisplatin have notable activity in treating bladder cancer. ^{1 2 3 4 5}

What safety data exists for CGC Therapy (Cabazitaxel, Gemcitabine, Cisplatin) in humans?

Studies have shown that Cabazitaxel, Gemcitabine, and Cisplatin have been evaluated for safety in bladder cancer treatments. Cisplatin is known to have side effects, but managing these can help avoid reducing or stopping treatment. Gemcitabine and Cisplatin together have been found to have a lower toxicity profile compared to older treatments. ^{1 4 5 6 7}

How is the CGC drug therapy for bladder cancer different from other treatments?

The CGC therapy is unique because it combines cabazitaxel, gemcitabine, and cisplatin and is administered directly into the bladder (intravesical), which is different from the standard systemic (throughout the body) treatments. This approach is being studied for its safety and effectiveness in patients whose bladder cancer has not responded to other treatments or has come back. ^{1 4 8 9 10}

What is the purpose of this trial?

The investigators intend to evaluate the safety and toxicity profile of intravesically administered multidrug regimen of Cabazitaxel, Cisplatin and Gemcitabine in treatment refractory Transitional Cell Carcinoma.The investigators propose to conduct a combined phase I trial to assess the safety, toxicity, and efficacy of a novel multidrug intravesical regimen consisting of Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the treatment of BCG resistant non-muscle invasive urothelial carcinoma of the bladder. This phase I trial will have a combined dose and cycle-escalation scheme with enrollment of up to 24 patients.

Research Team

Guarionex DeCastro, MD

Principal Investigator

Columbia University

Eligibility Criteria

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

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

A Single-arm Phase II Trial of Neoadjuvant Cabazitaxel and Cisplatin Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

State-of-the-art management of metastatic disease at initial presentation or recurrence. [2022]

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

Overview of gemcitabine triplets in metastatic bladder cancer. [2022]

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

A Phase I Trial of Intravesical Cabazitaxel, Gemcitabine and Cisplatin for the Treatment of Nonmuscle Invasive bacillus Calmette-Guérin Unresponsive or Recurrent/Relapsing Urothelial Carcinoma of the Bladder. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. [2021]

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

Management of cisplatin-associated toxicities in bladder cancer patients. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

[The efficacy and toxicity of gemcitabine and cisplatin chemotherapy in advanced/metastatic bladder urothelial carcinoma]. [2022]

8. Brazil pubmed.ncbi.nlm.nih.gov

Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma. [2022]

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

Relative efficacy of perioperative gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management of locally advanced urothelial carcinoma of the bladder. [2022]

10. Austria pubmed.ncbi.nlm.nih.gov

[Systemic oncological treatment of bladder cancer]. [2018]