Degarelix + Chemotherapy for Bladder Cancer

(TASUC-Neo Trial)

Overseen By Brown University Oncology Research Group

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brown University

Must be taking: Cisplatin, Gemcitabine

Must not be taking: Testosterone, Estrogen

Disqualifiers: Metastases, Cardiac disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is for patients who have bladder cancer that invades into the muscle wall of the bladder. The standard treatment for patients with muscle invasive bladder cancer is to give 4 cycles of chemotherapy with the drugs cisplatin and gemcitabine, then to do an operation to remove the bladder (cystectomy). In this study, the investigators will test participants' bladder cancer to see if their bladder cancer has a receptor for testosterone inside the bladder cancer cells. If it has the testosterone receptor participants will receive a medication called Degarelix that lowers testosterone levels in the blood. Degarelix will be given during the period that participants are receiving the standard of care chemotherapy drugs gemcitabine and cisplatin. The purpose of this study is to evaluate the effects, good and bad, of adding Degarelix to standard chemotherapy for patients with bladder cancer that have the testosterone receptor.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking testosterone, estrogen, or other sex hormone modifying agents.

What data supports the effectiveness of the drug combination Degarelix, Firmagon, Gemcitabine/Cisplatin, Gemzar/Cisplatin, Gemcitabine Hydrochloride/Cisplatin for bladder cancer?

Research shows that the combination of gemcitabine and cisplatin is effective in treating advanced bladder cancer, with response rates of 41% to 57% and comparable survival outcomes to other standard treatments, but with better safety and tolerability. ^{1 2 3 4 5}

Is the combination of Degarelix and chemotherapy safe for treating bladder cancer?

The combination of gemcitabine and cisplatin, which is part of the chemotherapy regimen, has been shown to have a favorable safety profile compared to older treatments, with fewer severe side effects like mouth sores and infections. Gemcitabine alone is generally well-tolerated, though it can cause low blood cell counts. ^{1 2 6 7 8}

What makes the Degarelix + Gemcitabine/Cisplatin drug unique for bladder cancer?

The Degarelix + Gemcitabine/Cisplatin drug is unique because it combines a hormone therapy (Degarelix) with chemotherapy (Gemcitabine/Cisplatin), potentially offering a novel approach to treating bladder cancer by targeting cancer cells through different mechanisms. This combination may provide a safer and more effective alternative to the traditional MVAC regimen, which is known for its high toxicity. ^{1 2 5 9 10}

Research Team

Sheldon L Holder, MD, PhD

Principal Investigator

Brown University

Eligibility Criteria

This trial is for adults over 18 with muscle-invasive bladder cancer that has a testosterone receptor. They must have good physical function and organ/marrow health, not be pregnant or breastfeeding, use non-hormonal contraception, and can't be on sex hormone treatments. Prior intravesical therapy is okay if it wasn't gemcitabine/platinum-based.

Inclusion Criteria

If you are a woman who could become pregnant, you need to have a negative pregnancy test within 7 days before joining the study.

I can care for myself but may not be able to do active work.

I am using or willing to use a highly effective non-hormonal birth control method for the study duration and six months after.

Exclusion Criteria

I am currently taking hormones like testosterone or estrogen.

I do not have any uncontrolled illnesses.

Patients who are pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Degarelix in combination with neoadjuvant gemcitabine and cisplatin for 4 cycles

12 weeks

4 visits (in-person) for chemotherapy, 3 visits (in-person) for Degarelix

Cystectomy

Participants undergo surgery to remove the bladder following chemotherapy

1 week

Follow-up

Participants are monitored for relapse-free survival and other outcomes

5 years

Year 1: q3 months, Year 2: q4 months, Year 3: q6 months, Years 4 and 5: annually

Treatment Details

Interventions

• Degarelix
• Gemcitabine/Cisplatin

Trial Overview The study tests adding Degarelix (lowers testosterone) to standard chemotherapy (Gemcitabine/Cisplatin) in patients whose bladder cancer cells have the testosterone receptor. The goal is to see how well this combination works compared to the standard treatment alone.

Participant Groups

Group I: Treatment Experimental Treatment 2 Interventions

In patients with androgen receptor positive (AR+), pT2 - pT4, N0 - N1, M0 urothelial cell carcinoma (UCC) of the bladder. The study medication, Degarelix, will be administered concurrently with neoadjuvant gemcitabine/cisplatin. * SOC Neoadjuvant Chemotherapy: Gemcitabine/Cisplatin 21-day cycles (4 cycles total) * Gemcitabine: 1000 mg/m2 (IV) Days 1 and 8 of each cycle * Cisplatin: 70 mg/m2 (if borderline renal function: 35 mg/m2) (IV) Day 1 of each cycle (if borderline renal function, days 1 and 8 of each cycle). * Study Medication: Degarelix (SC) Every 28-days (3 cycles total) Day -7 to -2 of cycle 1, then as defined in the study calendar (approximately q28 days). "initial dose is 240 mg administered as two 120 mg (3 mL) injections (SC), followed by subsequent doses at 80 mg (4 mL) administered as one injection (SC)

Gemcitabine/Cisplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Gemzar/Cisplatin for:

• Bladder cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Approved in European Union as Gemcitabine Hydrochloride/Cisplatin for:

• Bladder cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Approved in Canada as Gemcitabine/Cisplatin for:

• Bladder cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Legorreta Cancer Center at Brown University

Collaborator

Trials

1

Recruited

30+

Lifespan

Collaborator

Trials

43

Recruited

41,100+

Cures Within Reach

Collaborator

Trials

25

Recruited

2,100+

Findings from Research

In a phase III trial with 405 patients, the gemcitabine/cisplatin (GC) regimen showed comparable effectiveness to the standard MVAC regimen for advanced bladder cancer, with similar response rates and overall survival.

The GC regimen demonstrated significantly better safety and tolerability, with much lower rates of severe side effects like mucositis and neutropenic fever, suggesting it should be preferred as the standard treatment for advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in advanced bladder cancer. von der Maase, H.[2022]

The combination of gemcitabine and carboplatin shows a promising overall response rate of 60% in treating transitional cell carcinoma of the bladder, making it a potential alternative for patients who cannot tolerate cisplatin due to renal impairment or other comorbidities.

Given the high chemosensitivity of transitional cell carcinoma, this new treatment combination warrants further investigation in future phase III trials to confirm its efficacy and safety in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin in advanced urothelial cancer. Carles, J., Nogué, M.[2022]

In a study of 212 patients with muscle-invasive bladder cancer, both neoadjuvant gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) regimens resulted in similar pathologic complete response (pCR) rates, with 31% for GC and 29% for MVAC.

The analysis showed no significant difference in pCR rates or survival outcomes between the two treatment regimens, supporting the use of GC as a viable neoadjuvant option in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Galsky, MD., Pal, SK., Chowdhury, S., et al.[2022]

In a study of 22 patients with muscle-invasive bladder cancer, neoadjuvant chemotherapy using gemcitabine plus cisplatin achieved downstaging rates of 50% to pT0 and 63.6% to <pT2, which is comparable to the rates achieved with methotrexate, vinblastine, doxorubicin, and cisplatin in a comparator group of 9 patients.

Gemcitabine plus cisplatin demonstrated a better safety profile, with significantly lower rates of non-hematologic toxicity compared to the traditional chemotherapy regimen, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant gemcitabine plus cisplatin for muscle-invasive bladder cancer. Kaneko, G., Kikuchi, E., Matsumoto, K., et al.[2022]

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]

The study involved 78 patients with muscle invasive bladder cancer, assessing the tolerability of concurrent chemoradiation therapy with gemcitabine (GemX) after neoadjuvant chemotherapy (neoGemX), showing a high treatment completion rate of 95% for radiation and 96% for gemcitabine.

Toxicity levels were manageable, with no significant increase in bowel or urinary toxicity between the neoGemX and GemX groups, indicating that prior neoadjuvant chemotherapy does not add extra risk when followed by GemX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Concurrent Chemoradiation Therapy With Gemcitabine (GemX), With and Without Prior Neoadjuvant Chemotherapy, in Muscle Invasive Bladder Cancer. Thompson, C., Joseph, N., Sanderson, B., et al.[2022]

Gemcitabine has shown significant effectiveness in treating superficial BCG-resistant bladder cancer and is a viable option for BCG-intolerant patients through intravesical instillation.

In advanced bladder cancer, the combination of gemcitabine and cisplatin is recognized as a standard first-line treatment, making gemcitabine a flexible choice for various patient conditions, including those who are unfit for more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in bladder cancer. El Karak, F., Flechon, A.[2022]

In a study of 33 patients with advanced urothelial carcinoma who had previously failed M-VAC chemotherapy, the combination of gemcitabine and cisplatin (GC) resulted in an overall response rate of 39.4%, with 6% achieving complete responses and 33.3% partial responses.

Despite significant side effects like grade 3-4 neutropenia in 66.7% of patients, there were no fatal side effects, suggesting that GC chemotherapy is a feasible option that may offer a survival benefit, with a mean survival time of 10.5 months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of gemcitabine plus cisplatin regimen for patients with advanced urothelial carcinoma after failure of M-VAC regimen. Gondo, T., Ohori, M., Hamada, R., et al.[2022]

The combination of paclitaxel, cisplatin, and gemcitabine demonstrated a high overall response rate of 77.6% in 61 patients with advanced transitional-cell carcinoma, indicating strong antitumor activity.

The recommended doses for further studies were established as 80 mg/m² of paclitaxel and 1,000 mg/m² of gemcitabine, with manageable toxicity, although significant side effects like grade 3 neutropenia were observed in 55% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. Bellmunt, J., Guillem, V., Paz-Ares, L., et al.[2022]

The gemcitabine and carboplatin combination treatment for advanced transitional cell carcinoma (TCC) showed a 56.1% overall response rate, making it an effective alternative to standard cisplatin-based therapies, especially for patients with impaired renal function or poor performance status.

Despite significant hematologic toxicities, such as neutropenia and anemia, the treatment had an acceptable safety profile, allowing for administration in elderly patients and those with other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. Nogué-Aliguer, M., Carles, J., Arrivi, A., et al.[2022]

References

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

Gemcitabine in advanced bladder cancer. [2022]

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

Gemcitabine/carboplatin in advanced urothelial cancer. [2022]

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

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant gemcitabine plus cisplatin for muscle-invasive bladder cancer. [2022]

5. Brazil pubmed.ncbi.nlm.nih.gov

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

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

Tolerability of Concurrent Chemoradiation Therapy With Gemcitabine (GemX), With and Without Prior Neoadjuvant Chemotherapy, in Muscle Invasive Bladder Cancer. [2022]

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

Gemcitabine in bladder cancer. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

The efficacy and safety of gemcitabine plus cisplatin regimen for patients with advanced urothelial carcinoma after failure of M-VAC regimen. [2022]

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

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. [2022]

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

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. [2022]