Trial Summary
What is the purpose of this trial?This research study is studying the effects of adding a certain type of immunotherapy to standard bladder-directed radiation as a treatment for muscle-invasive urothelial carcinoma of the bladder.
The drug in this study is: Avelumab (also known as BAVENCIO®)
Do I have to stop taking my current medications for the trial?The trial requires you to stop any current chemotherapy, biologic, or hormonal therapy for cancer treatment. You also cannot use immunosuppressive medications, except for certain low-dose steroids or specific premedications. The protocol does not specify other medications, but you should discuss your current medications with the trial team.
Is Avelumab, a drug used with radiation, a promising treatment for bladder cancer?Yes, Avelumab combined with radiation is promising for bladder cancer. It helps the immune system fight cancer cells and has been shown to improve survival in patients with advanced bladder cancer.25678
What safety data exists for Avelumab and Radiation in bladder cancer treatment?Avelumab, also known as Bavencio, has been evaluated for safety in several studies involving patients with advanced urothelial carcinoma. In a phase Ib study, common treatment-related adverse events included fatigue, infusion-related reactions, and nausea, with serious adverse events occurring in a small percentage of patients. Avelumab was generally well tolerated, with durable responses and prolonged survival observed. In a broader analysis of 21 trials, Avelumab monotherapy showed a 73.78% incidence of all-grade treatment-related adverse events, with 14.44% being high-grade. The data suggests Avelumab has a manageable safety profile, but specific safety data for the combination with radiation therapy in bladder cancer is not detailed in the provided research.12468
What data supports the idea that Avelumab + Radiation for Bladder Cancer is an effective treatment?The available research shows that Avelumab, when used as a maintenance treatment after initial chemotherapy for advanced bladder cancer, can help prolong the life of patients. Although the specific combination of Avelumab and radiation for bladder cancer isn't directly discussed, Avelumab alone has shown promising results in improving survival rates for patients with advanced bladder cancer. This suggests that Avelumab could be an effective part of a treatment plan for bladder cancer.23689
Eligibility Criteria
Adults with muscle-invasive bladder cancer who can't receive cisplatin chemotherapy due to certain health issues or personal choice. They must have normal organ/marrow function, not be pregnant, agree to use contraception if there's a risk of conception, and have no history of severe allergies to monoclonal antibodies or other exclusion criteria like active infections.Inclusion Criteria
I am of child-bearing age and my pregnancy test was negative.
I can take care of myself but might not be able to do active work.
My organs and bone marrow are functioning normally.
Exclusion Criteria
I have not had major surgery in the last 30 days, except for TURBT.
I am not currently on any cancer treatments like chemotherapy.
I have received IV therapy for bladder cancer.
My scans show cancer has spread to my lymph nodes or other areas.
I have had radiation therapy to my pelvic area before.
I have had an organ or stem-cell transplant.
I am breastfeeding and not willing to stop during and for a month after treatment.
I am currently on IV antibiotics for an infection.
I do not have serious heart problems or a recent stroke or heart attack.
My bladder biopsy shows small cell cancer.
Treatment Details
The trial is testing the combination of Avelumab (an immunotherapy drug) with standard radiation therapy for treating muscle-invasive urothelial carcinoma. The goal is to see if adding Avelumab improves treatment outcomes compared to radiation alone.
1Treatment groups
Experimental Treatment
Group I: Avelumab and Bladder-Directed RadiationExperimental Treatment2 Interventions
* Avelumab will be administered every 2 weeks intravenously for 6 doses unless there is unacceptable toxicity
* Two radiation dose regimens are allowed, and the regimen selected is at the discretion of the treating radiation oncologist
Avelumab is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Bavencio for:
- Merkel cell carcinoma
- Renal cell carcinoma
- Urothelial carcinoma
🇺🇸 Approved in United States as Bavencio for:
- Merkel cell carcinoma
- Renal cell carcinoma
- Urothelial carcinoma
🇯🇵 Approved in Japan as Bavencio for:
- Merkel cell carcinoma
- Renal cell carcinoma
- Urothelial carcinoma
Find a clinic near you
Research locations nearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
Dana-Farber Cancer InstituteBoston, MA
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Who is running the clinical trial?
Dana-Farber Cancer InstituteLead Sponsor
PfizerIndustry Sponsor
References
Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. [2022]Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.
Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. [2022]The approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients.
Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis. [2021]Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ≥2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma.
Efficacy and safety profile of avelumab monotherapy. [2021]Avelumab can kill cancer cells through immune checkpoint inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we analyzed the clinical efficacy and adverse events (AEs) in 3935 cancer patients from 21 trials. Compared with conventional treatment, avelumab monotherapy was associated with more tumor responses and less AEs. The pooled objective response rate was 14.18 % (95 % CI, 10.68 %-18.08 %). More PD-L1 positive patients responded to avelumab monotherapy compared to PD-L1 negative patients. The overall incidence was 73.78 % for all-grade treatment-related AE (TRAE), 14.44 % for high-grade TRAE, 6.07 % for serious adverse event, 0.44 % for fatal adverse event, 17.86 % for all-grade immune-related AE (irAE), and 3.22 % for high-grade irAE. In summary, avelumab monotherapy presents an active anti-tumor activity, shows no sign of increased toxicity due to the ADCC. These characteristics provide rational for further application of avelumab in cancer treatment.
Avelumab in locally advanced or metastatic urothelial carcinoma. [2022]Outcomes for patients with advanced or metastatic urothelial carcinoma (UC) remain poor. Targeting the programmed death ligand-1 (PD-(L)1) immune checkpoint pathway has emerged as a useful target in patients with UC. Avelumab is a PD-L1 inhibitor, resulting in restoration of a cytotoxic, antitumor T cell response. Results from the JAVELIN bladder 100 trial has resulted in a new standard of care of platinum-based chemotherapy sequenced by maintenance avelumab in advanced or metastatic UC.
Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">First-line therapy for treatment of advanced urothelial carcinoma includes combination platinum-based chemotherapies, though resistance and long-term toxicity concerns to these regimens cause limitations in progression-free survival and overall survival. Maintenance treatment with an alternative agent such as the PD-L1 inhibitor, avelumab (Bavencio®), after initial chemotherapy has been shown to prolong overall survival. The aim of this review is to provide a landscape clinical use of avelumab in the treatment of advanced urothelial carcinoma with a focus on patient selection and outcomes.
Cost-Effectiveness of Avelumab Maintenance Therapy Plus Best Supportive Care vs. Best Supportive Care Alone for Advanced or Metastatic Urothelial Carcinoma. [2022]Avelumab (MSB0010718C) is a fully human anti-programmed cell death ligand 1(PD-L1) antibody against PD-L1 interactions and enhances immune activation against tumor cells in the meantime. Avelumab has been approved for locally advanced or metastatic urothelial cancer (mUC) after disease progression in several countries. We therefore conducted this study to evaluate the cost-effectiveness of avelumab maintenance therapy for advanced or mUC from the perspective of the United States (US) and China payer.
Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. [2023]To develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC).
Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]To evaluate the safety and pathologic complete response (pCR) rate of radiation therapy with atezolizumab as bladder-preserving therapy for invasive bladder cancer.