Bladder CancerPhase 2NCT03747419
Avelumab and Radiation in Muscle-Invasive Bladder Cancer
A Phase 2 study testing Avelumab and Radiation in people with Bladder Cancer and Muscle Invasive Bladder Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
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®) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Muscle Invasive Bladder Cancer
- What is being tested?
- Avelumab and Radiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Dec 2018to 24 Feb 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed transitional cell (urothelial) carcinoma of the bladder that is invasive into the muscularis propria (≥T2 disease) within 6 months of enrollment date. The presence of variant histologies (squamous, adenocarcinoma, micropapillary, etc.) is allowed. Note: A prior diagnosis of non-muscle-invasive bladder cancer (≤T1) managed with transurethral resection with or without intravesicular therapy (now with muscle invasion) is allowed.
- Inability to receive cisplatin-based chemotherapy, as defined by creatinine clearance <60 ml/min, ECOG PS ≤2, grade 2 or higher hearing loss, NYHA class 3 or higher, neuropathy (grade 2 or higher), or patient refusal to receive cisplatin-based chemotherapy.
- Additional Inclusion Criteria:
- Male or female subjects aged ≥18 years
- ECOG performance status ≤2 or Karnofsky score ≥60% (see Appendix A)
- Life expectancy of greater than 1 year
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- Demonstrate normal organ and marrow function
- Estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula.
- Women of child-bearing age must have a negative serum pregnancy test at screening.
- Women of child-bearing potential and men must agree to use a highly effective method of contraception (hormonal or barrier method of birth control, or abstinence) beginning prior to study entry, for the duration of study participation, and for at least 30 days after last avelumab treatment administration if the risk of conception exists
- Ability to start study treatment (first cycle of Avelumab) within 1-8 weeks of the most recent pre-study TURBT.
- Ability to understand and willingness to sign a written informed consent document
Who cannot join
- Prior intravenous therapy for treatment of bladder cancer
- Prior pelvic radiation
- Any component of small cell histology in the bladder biopsy
- Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroid, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
- History of another malignancy within 5 years prior to randomization except for: non-muscle-invasive bladder cancer (i.e., ≤T1), completely resected basal cell or squamous cell skin cancer, completed resected carcinoma-in-situ of any site, or localized prostate cancer managed definitively with a non-radiation based approach.
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- Additional Exclusion Criteria:
- Evidence of lymph node involvement or metastatic disease on CT of the chest, abdomen, and pelvis. To be considered positive, a lymph node must measure >15 mm in short axis.
- Clinically significant (i.e. active) cardiovascular disease: symptomatic congestive heart failure (≥ New York Heart Association Classification Class II), unstable angina pectoris, serious cardiac arrhythmia requiring medication, or CVA/stroke/MI (< 6 months prior to enrollment)
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
- Breast feeding women who are unwilling to stop breastfeeding during treatment and for at least one month after the duration of treatment
- Patients with known history of testing positive for HIV or known acquired immunodeficiency syndrome
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- Active infection requiring intravenous antibiotic therapy
- Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
- Major surgery within the last 30 days (with the exception of TURBT).
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
- Prior organ transplantation including allogenic stem-cell transplantation
- Patient is unwilling to stop (or wishes to start) taking herbal and natural remedies that may have immune-modulating effects during the study period
- Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
- Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Pregnant women are excluded from this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02215
About this study
Official title: A Phase 2 Study of Avelumab in Combination With Bladder-Directed Radiation in Cisplatin-Ineligible Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder
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®)
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved the use of avelumab and bladder-directed radiation together for this specific disease but avelumab has been approved for other uses.
While bladder-directed radiation is a standard treatment option for muscle-invasive urothelial carcinoma of the bladder, the use of avelumab in combination with bladder radiation in patients with urothelial carcinoma of the bladder is investigational. Radiation is used in the treatment of muscle-invasive bladder cancer, and avelumab has been approved by the FDA in patients with more advanced stages of this disease. Avelumab is a form of immunotherapy, which means it is designed to help the immune system fight cancer cells together with standard cancer treatments like radiation. Avelumab is currently approved by the FDA for the treatment of metastatic Merckel cell carcinoma (mMCC) and platinum-refractory metastatic urothelial carcinoma.
The purpose of this study is to test whether the combination of immunotherapy and bladder directed radiation is effective in treating muscle-invasive bladder cancer. The study will also measure other outcomes such as participant's overall health and quality of life during and after treatment. In addition, the investigators will determine if certain biomarkers are correlated with outcomes following treatment with immunotherapy and radiation.
- Conditions
- Bladder Cancer, Muscle Invasive Bladder Cancer
- Keywords
- Bladder Cancer, Bladder Carcinoma, Carcinoma of Bladder, Carcinoma of the Bladder, MIBC, Muscle Invasive Bladder Cancer, Muscle-Invasive Urothelial Carcinoma of the Bladder, Immunotherapy, Avelumab, Radiation and Immunotherapy, No cisplatin, Cisplatin Ineligible, Cisplatin-Ineligible, T2 Disease, T3 Disease, T4 Disease, squamous bladder cancer, adenocarcinoma bladder cancer, micropapillary bladder cancer, Inability to receive cisplatin-based chemotherapy
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Also called Bavencio
Avelumab is a form of immunotherapy, which means it is designed to help the patient's immune system kill cancer cells.
RadiationRadiation
Cancer treatment that uses ionizing radiation to kill cancer cells.
| Study group | Role | What they receive |
|---|---|---|
| Avelumab and Bladder-Directed Radiation | Experimental | * 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 Receives: Drug: Avelumab; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Clinical Response Rate
Measured by the complete clinical response rate at 3 months following completion of radiation, followed by every 3 months until 2 years after registration, then every 6 months up to a maximum of 3 years after registration. Clinical response is assessed by cystoscopy, urine cytology, and CT Chest/Abdomen/Pelvis. No evidence of disease on these assessments at a given time point suggests a Complete Clinical Response at that time point.
Measured: 3 months following completion of radiation; then every 3 months until 2 years after registration; then every 6 months up to a maximum of 3 years after registration
Secondary outcomes (5)
Overall Survival
Overall Survival (OS)
Measured: 3 years
Progression Free Survival
Progression Free Survival (PFS) as assessed by imaging, cystoscopy, and cytology.
Measured: 3 years
Metastases-free Survival
Metastases-free survival (MFS) as assessed by imaging.
Measured: 3 years
Locoregional Recurrence Rate
Locoregional recurrence rate (LRR) as assessed by imaging.
Measured: 3 years
Change in Quality of Life Outcomes
Quality of Life Outcomes (QoL) as measured by patient report on questionnaires. Patients are given a statement and must assign a number to assess how the statement applies to them in the past 7 days. 0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; 4=Very much. QoLs were collected at baseline, end of radiation, 3 months post-radiation completion, then every 3 months through year 2 after treatment.
Median scores and interquartile ranges were calculated for baseline, 3 months post-radiation completion, and 2 years post-treatment. 3 months post-RT was selected to coincide with the primary outcome timeframe. Year 2 was selected due to the number of patients that reached this point during follow up; most patients did not surpass year 2.
Higher score means worse outcome for questions regarding diarrhea, urinary frequency \& burning, and being bothered by treatment. Higher score means better outcome for questions regarding being content with quality of life and control over bowels.
Measured: Baseline; 3 months following completion of radiation; 2 years after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2018
- Study start13 Dec 2018
- Primary completion24 Feb 2025
- Study completion24 Feb 2025
Why it stopped: In agreement with the drug sponsor and the institution, the trial has been terminated due to slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- EMD Serono
- Responsible party
- Principal investigator, Kent Mouw, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Kent Mouw, MD, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03747419
- Sponsor's protocol ID
- 18-464
- Status last verified
- Sep 2025
- First submitted
- 16 Nov 2018
- Last updated
- 31 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Avelumab in Combination With Bladder-Directed Radiation in Cisplatin-Ineligible Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder
- ClinicalTrials.gov ID
- NCT03747419
- Acronym / sponsor ID
- 18-464
- Conditions
- Bladder Cancer, Muscle Invasive Bladder Cancer
- Keywords
- Bladder Cancer, Bladder Carcinoma, Carcinoma of Bladder, Carcinoma of the Bladder, MIBC, Muscle Invasive Bladder Cancer, Muscle-Invasive Urothelial Carcinoma of the Bladder, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: In agreement with the drug sponsor and the institution, the trial has been terminated due to slow accrual.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- EMD Serono
- Study start
- 13 Dec 2018 (actual)
- Primary completion
- 24 Feb 2025 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 20 Nov 2018 (actual)
- Results
- Posted 31 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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®)
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved the use of avelumab and bladder-directed radiation together for this specific disease but avelumab has been approved for other uses.
While bladder-directed radiation is a standard treatment option for muscle-invasive urothelial carcinoma of the bladder, the use of avelumab in combination with bladder radiation in patients with urothelial carcinoma of the bladder is investigational. Radiation is used in the treatment of muscle-invasive bladder cancer, and avelumab has been approved by the FDA in patients with more advanced stages of this disease. Avelumab is a form of immunotherapy, which means it is designed to help the immune system fight cancer cells together with standard cancer treatments like radiation. Avelumab is currently approved by the FDA for the treatment of metastatic Merckel cell carcinoma (mMCC) and platinum-refractory metastatic urothelial carcinoma.
The purpose of this study is to test whether the combination of immunotherapy and bladder directed radiation is effective in treating muscle-invasive bladder cancer. The study will also measure other outcomes such as participant's overall health and quality of life during and after treatment. In addition, the investigators will determine if certain biomarkers are correlated with outcomes following treatment with immunotherapy and radiation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avelumab and Bladder-Directed Radiation | Experimental | Drug: Avelumab, Radiation: Radiation* 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed transitional cell (urothelial) carcinoma of the bladder that is invasive into the muscularis propria (≥T2 disease) within 6 months of enrollment date. The presence of variant histologies (squamous, adenocarcinoma, micropapillary, etc.) is allowed. Note: A prior diagnosis of non-muscle-invasive bladder cancer (≤T1) managed with transurethral resection with or without intravesicular therapy (now with muscle invasion) is allowed.
- Inability to receive cisplatin-based chemotherapy, as defined by creatinine clearance <60 ml/min, ECOG PS ≤2, grade 2 or higher hearing loss, NYHA class 3 or higher, neuropathy (grade 2 or higher), or patient refusal to receive cisplatin-based chemotherapy.
- Male or female subjects aged ≥18 years
- ECOG performance status ≤2 or Karnofsky score ≥60% (see Appendix A)
- Life expectancy of greater than 1 year
Key exclusion criteria (22 listed)
- Prior intravenous therapy for treatment of bladder cancer
- Prior pelvic radiation
- Any component of small cell histology in the bladder biopsy
- Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroid, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvelumabAlso: BavencioAvelumab is a form of immunotherapy, which means it is designed to help the patient's immune system kill cancer cells. | Drug | Avelumab and Bladder-Directed Radiation |
| RadiationCancer treatment that uses ionizing radiation to kill cancer cells. | Radiation | Avelumab and Bladder-Directed Radiation |
Primary outcome
Complete Clinical Response Rate
Time frame: 3 months following completion of radiation; then every 3 months until 2 years after registration; then every 6 months up to a maximum of 3 years after registration
Measured by the complete clinical response rate at 3 months following completion of radiation, followed by every 3 months until 2 years after registration, then every 6 months up to a maximum of 3 years after registration. Clinical response is assessed by cystoscopy, urine cytology, and CT Chest/Abdomen/Pelvis. No evidence of disease on these assessments at a given time point suggests a Complete Clinical Response at that time point.
5 secondary outcomes
Overall Survival
Time frame: 3 years
Progression Free Survival
Time frame: 3 years
Metastases-free Survival
Time frame: 3 years
Locoregional Recurrence Rate
Time frame: 3 years
Change in Quality of Life Outcomes
Time frame: Baseline; 3 months following completion of radiation; 2 years after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kent Mouw, MD, PhD principal investigator
Brigham and Women's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab and Radiation in people with Bladder Cancer and Muscle Invasive Bladder Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Clinical Response Rate (time frame: 3 months following completion of radiation; then every 3 months until 2 years after registration; then every 6 months up to a maximum of 3 years after registration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025.