Durvalumab + Chemo/Radiation for Bladder Cancer

Not currently recruiting at 257 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressive medications

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 6.5-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding an immunotherapy drug called durvalumab to standard chemotherapy and radiation can more effectively treat bladder cancer that has spread to the lymph nodes. Standard treatments aim to stop cancer growth, while durvalumab helps the immune system attack cancer cells. The trial includes different groups: some receive the combination of all three treatments, while others receive only the standard treatment for comparison. Individuals with bladder cancer that has spread to nearby lymph nodes, but not to other parts of the body, might be suitable candidates, especially if they haven't previously undergone radiation in the pelvic area. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering a chance to benefit from innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that you must not have used immunosuppressive medication within 14 days before starting durvalumab, with some exceptions like certain steroids. It's best to discuss your specific medications with the trial team.

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

In earlier studies, durvalumab has proven to be generally safe. Researchers tested it in patients with various solid cancers, including bladder cancer, and most patients tolerated it well. Common side effects included tiredness and nausea, typically mild to moderate.

When combined with radiation therapy, durvalumab has been safe for patients with muscle-invasive bladder cancer. The combination did not cause unexpected side effects, and most patients managed the treatment without serious issues.

However, since this trial is in Phase 2, the research process is still in its early stages. More information is needed to confirm the safety of durvalumab when used with chemotherapy and radiation therapy. Nonetheless, the results so far are encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about durvalumab for bladder cancer because it offers a unique approach by harnessing the body's immune system to target cancer cells. Unlike traditional chemotherapy and radiation, which directly attack cancer cells, durvalumab is an immune checkpoint inhibitor that blocks the PD-L1 protein. This action prevents cancer cells from evading the immune response, potentially leading to more effective and lasting cancer control. Additionally, incorporating durvalumab with standard chemoradiation could enhance overall treatment efficacy, offering new hope for patients with bladder cancer.

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

Research has shown that durvalumab, a type of immunotherapy, may help treat bladder cancer. In this trial, some participants will receive durvalumab combined with chemotherapy and radiation therapy. For patients with urothelial carcinoma, a common form of bladder cancer, durvalumab has been effective, particularly in those with a specific protein called PD-L1 that the drug targets. Studies have found that when used with chemotherapy and radiation, durvalumab can increase survival rates. Specifically, the chances of survival at 6, 9, and 12 months were 64%, 57%, and 55%, respectively. This suggests that adding durvalumab to standard treatments might control the cancer better than using only chemotherapy and radiation, which is another treatment arm in this trial. ^{2 3 5 6 7}

Who Is on the Research Team?

Monika Joshi

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with bladder cancer that has spread to lymph nodes but not elsewhere. They must have good physical function, no prior pelvic radiation, and acceptable blood counts and organ function. HIV-positive patients on effective therapy can join. Those with a history of certain cancers or autoimmune diseases, active infections like tuberculosis or hepatitis, or who are pregnant cannot participate.

Inclusion Criteria

I agree to have a CT scan for treatment planning.

I have never had radiation therapy to my pelvic area.

I meet the criteria for adjuvant durvalumab treatment.

Exclusion Criteria

I haven't had any live vaccines in the last 30 days.

You have a history of a weak immune system from birth.

I do not have serious liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo chemoradiation with or without durvalumab for bladder cancer

6.5-8 weeks

Multiple visits for radiation and chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Every 12 weeks for 1 year, every 6 months for year 2, then annually for years 3-4

Extension

Participants who achieve clinical CR or benefit may receive additional durvalumab treatment

6 cycles of 28 days each

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Doxorubicin Hydrochloride
• Durvalumab
• Fluorouracil
• Gemcitabine Hydrochloride
• Methotrexate
• Mitomycin
• Radiation Therapy
• Vinblastine Sulfate

Trial Overview The INSPIRE study is testing if adding the immunotherapy drug Durvalumab to standard chemotherapy (Cisplatin) and radiation improves treatment response in bladder cancer that's reached lymph nodes. The goal is to see if this combination helps shrink tumors better than chemo and radiation alone.

How Is the Trial Designed?

Group I: Step 2, Arm E (durvalumab) Experimental Treatment 6 Interventions

Patients previously randomized to Arm C (chemoradiation and durvalumab) who achieve clinical CR or clinical benefit receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

Group II: Step 1, Arm C (durvalumab, radiation therapy, chemotherapy) Experimental Treatment 11 Interventions

Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; or cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

Group III: Step 1, Arm D (radiation therapy, chemotherapy) Active Control 10 Interventions

Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; or cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

Group IV: Step 2, Arm F (observation) Active Control 6 Interventions

Patients previously randomized to Arm D (chemoradiation) who achieve clinical CR or clinical benefit undergo observation undergo observation. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Combination chemotherapy for metastatic bladder cancer, particularly the MVAC regimen, shows the highest effectiveness with complete response rates of 30-40%.

Chemotherapy is primarily used for palliative care in metastatic cases, but it can also serve as neoadjuvant treatment to shrink tumors before surgery, potentially preserving the bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Why use chemotherapy in cancer of the bladder? What are the initial limitations]. Maraninchi, D., Viens, P.[2013]

In a randomized phase III trial involving 220 patients with inoperable or metastatic urothelial carcinoma, the MVAC regimen demonstrated superior response rates (54.2% vs. 37.4%) and longer median time to progression (9.4 months vs. 6.1 months) compared to the docetaxel and cisplatin (DC) combination.

While MVAC was more effective, it also resulted in higher rates of severe side effects, such as neutropenia and neutropenic sepsis, although the toxicity was lower than previously reported for MVAC without G-CSF support, suggesting that G-CSF makes MVAC a safer option for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. Bamias, A., Aravantinos, G., Deliveliotis, C., et al.[2018]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In a study of 45 patients with high-risk bladder cancer, the combination of transurethral resection of the bladder tumor (TURB) with concurrent cisplatin, 5-fluorouracil (5-FU), and radiation therapy resulted in an impressive 87% complete response rate, with 64% of patients remaining tumor-free after treatment.

The treatment protocol demonstrated acceptable safety, with only 10% experiencing severe hematologic toxicity and a 5-year survival rate of 54% with preserved bladder, indicating its efficacy and potential as a viable option for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil. Rödel, C., Grabenbauer, GG., Kühn, R., et al.[2019]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27269937/

Safety and Efficacy of Durvalumab (MEDI4736), an ... - PubMed Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.67.9761

Safety and Efficacy of Durvalumab (MEDI4736), an Anti– ... Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6452813/

Durvalumab for the management of urothelial carcinoma The median time to response was 6.3 weeks (95% CI, 5.6–12.1 weeks) in the 13 responding patients, and median duration of response has not been reached (range, ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.778

Feasibility and safety results from RAD-IO Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02516241

NCT02516241 | Study of MEDI4736 (Durvalumab) With or ... This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06503614

Study Details | NCT06503614 | A Trial of Durvalumab ... This is a phase 2 open-label two cohort study of durvalumab plus monalizumab in patients with BCG-unresponsive or BCG-exposed CIS NMIBC.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...