Avelumab and Radiation in Muscle-Invasive Bladder Cancer

NCT03747419 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-464
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief 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®)

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  3 years

• Progression Free Survival

  3 years

• Metastases-free Survival

  3 years

• Locoregional Recurrence Rate

  3 years

• Change in Quality of Life Outcomes

  Baseline; 3 months following completion of radiation; 2 years after treatment

Study Arms (1)

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

Drug: Avelumab; Radiation: Radiation

Interventions

Avelumab DRUG

Avelumab is a form of immunotherapy, which means it is designed to help the patient's immune system kill cancer cells.

Also known as: Bavencio

Avelumab and Bladder-Directed Radiation

Radiation RADIATION

Cancer treatment that uses ionizing radiation to kill cancer cells.

Avelumab and Bladder-Directed Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• EMD Serono: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

avelumab; Radiation

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Limitations and Caveats

Early termination was due to slow accrual. 14 out of 24 patients were accrued during the duration of the study.

Results Point of Contact

• Title: Kent Mouw
• Organization: Dana-Farber Cancer Institute

kent_mouw@dfci.harvard.edu

6176325734

Study Officials

• Kent Mouw, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 20, 2018
• Study Start: December 13, 2018
• Primary Completion: February 24, 2025
• Study Completion: February 24, 2025
• Last Updated: October 31, 2025
• Results First Posted: October 31, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)