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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating bladder cancer that has spread into the muscle wall. It tests whether adding Degarelix—a drug that lowers testosterone levels—can enhance the effects of standard chemotherapy treatments like gemcitabine and cisplatin. The focus is on patients whose cancer cells have a testosterone receptor. Those with muscle-invasive bladder cancer and this specific receptor, who are eligible for standard chemotherapy, might be a good fit for the study. 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 new treatment approach.

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.

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

Research shows that Degarelix, used in this study, is generally well-tolerated. This medication lowers testosterone levels and has approval for treating prostate cancer. Many patients find its monthly injection schedule convenient.

For the chemotherapy drugs gemcitabine and cisplatin, studies indicate they are standard treatments for bladder cancer. These drugs are widely used and effective. Some side effects, such as nausea or low blood counts, may occur, but they are common and usually manageable.

Overall, research suggests that combining Degarelix with these chemotherapy drugs is promising, with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for bladder cancer, which typically involves chemotherapy with drugs like Gemcitabine and Cisplatin, the new treatment combines these with Degarelix, a medication that targets androgen receptors. Degarelix is unique because it works by suppressing testosterone, which may play a role in the growth of certain bladder cancers. Researchers are excited about this approach because it could enhance the effectiveness of chemotherapy by targeting the cancer cells in a new way, potentially leading to better outcomes for patients with androgen receptor-positive bladder cancer.

What evidence suggests that adding Degarelix to standard chemotherapy could be effective for bladder cancer?

Research shows that combining gemcitabine and cisplatin effectively treats muscle-invasive bladder cancer. Studies indicate that this chemotherapy combination is safe and often results in the cancer shrinking or disappearing before surgery. In this trial, Degarelix, a drug that lowers testosterone, will be added to the chemotherapy regimen. Early research suggests that blocking male hormone signals, as Degarelix does, can help fight bladder cancer. Although the use of Degarelix is still under investigation, it appears promising because it targets a pathway that aids cancer growth. ^{1 2 3 5 6}

Who Is on the Research Team?

Sheldon L Holder, MD, PhD

Principal Investigator

Brown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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 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 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]

Citations

1. bcan.org bcan.org/clinicaltrials/targeting-androgen-signaling-in-urothelial-cell-carcinoma-neoadjuvant/

Targeting Androgen Signaling in Urothelial Cell Carcinoma 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10886823/

Roles of Androgen Receptor Signaling in Urothelial ... Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development.

3. journals.lww.com journals.lww.com/cur/fulltext/2021/12000/patients_and_physician_satisfaction_of_degarelix.5.aspx

Patients and physician satisfaction of Degarelix in... Monthly Degarelix administration was considered a satisfactory frequency by 82% (173/211) of patients at 6 months and 83.6% (117/140) at 12 months.

4. ferring.com ferring.com/new-data-demonstrating-long-term-benefits-of-firmagon-degarelix-for-advanced-hormone-dependant-prostate-cancer-published-in-the-journal-of-urology/

New data demonstrating long-term benefits of FIRMAGON ... At a median follow up of 27.5 months the data showed that the risk of PSA PFS had decreased (p=0.003). Longer PSA PFS is desirable as it is ...

5. urotoday.com urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/77091-new-data-from-a-pooled-analysis-shows-improved-overall-survival-for-prostate-cancer-patients-treated-with-firmagon-degarelix-compared-to-lhrh-agonists.html

New data from a pooled analysis shows improved overall ... Bladder Cancer ... New data from a pooled analysis shows improved overall survival for prostate cancer patients treated with FIRMAGON® (degarelix) ...

6. ema.europa.eu ema.europa.eu/en/documents/variation-report/firmagon-h-c-000986-ii-0039-g-epar-assessment-report-variation_en.pdf

Firmagon, INN-degarelix - EMA This meta-analysis was conducted to compare the outcomes of patients who have received external beam radiotherapy and hormone therapy, alone or ...