Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer

NCT03171025 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCI100769
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 2, single arm, open label trial to evaluate the rate of failure free survival at 2 years after start of chemoradiation with adjuvant nivolumab in adult subjects who undergo chemoradiation for localized bladder cancer.

Conditions

Bladder Cancer

Keywords

Muscle Invasive

Outcome Measures

Primary Outcomes (1)

• Two-year rate of failure-free survival (FFS)

  The definition of failure will include loco-regional recurrence, and distant recurrence. The primary endpoint of the FFS will be determined based on disease recurrence date defined as the time between the start date of chemoradiation and the date of first recurrence or non-cancer related death.

  2 years

Secondary Outcomes (8)

• Rate of failure-free survival at two years in subjects with intact bladder (FFSIB).

  2 years

• Rate of failure free survival at two years on nivolumab

  2 years

• Rate of acute and late grade 2 or higher treatment related Genitourinary, Gastrointestinal, hematologic and immune related adverse events.

  Patient safety will be evaluated throughout the treatment period and follow up (treatment with Nivolumab is expected to last 1 year for each patient and follow up for 2 years)

• Effect of treatment on Quality of Life

  Quality of life questionnaires done every 3 months while patients are on treatment for 1 year

• Cystoscopic Local Control

  Done at 6 months, 1 year and 2 years

Study Arms (1)

Nivolumab, all patients

EXPERIMENTAL

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab at a dose of 480 mg will be administered as an IV infusion over 60 minutes every 4 weeks until disease recurrence or discontinuation due to unacceptable toxicity for a maximum of 12 treatments over an expected duration of 1 year.

Nivolumab, all patients

Eligibility Criteria

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

You may qualify if:

• Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4b, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy.
• Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation. Patients who have M1 disease at any time prior to start of treatment are not eligible.
• Staging is determined prior to chemoradiation
• Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as but not limited to comorbidities, age, surgical risk or patient refusal to undergo radical cystectomy. Patients who refuse to undergo radical cystectomy are not required to be evaluated by a urologic oncologist.
• Patients must have histologically proven primary adenocarcinoma, transitional, squamous-cell, or sarcomatoid carcinoma primary of the bladder, urethra, or lower ureter.
• Treating investigator has determined that the patients are not a candidate for radical cystectomy. Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as, but not limited to, comorbidities, age, surgical risk, or patient refusal to undergo radical cystectomy.
• Tumor tissue from the most recently resected site of disease (preferable) or from the transurethral resection that yielded the initial muscle invasive diagnosis must be provided for biomarker correlative analyses. Enrollment is permitted if adequate archived tissue is unavailable.
• Patients must have received systemic radiosensitizing chemotherapy with definitive pelvic radiation therapy. Patients may have received partial amount of chemotherapy and radiation (both) to be eligible.
• Platinum based chemotherapy prior to chemoradiation is permitted but not mandatory
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
• Age ≥18.
• Adequate bone marrow function White Blood Cell (WBC) \> 2000/µl, neutrophils \>1500/µl, Hemoglobin \>9.0 g/dl.
• Serum bilirubin and aminotransferase values less than 1.5 times the upper limit of the normal range
• Creatinine clearance of 20 ml/min or greater as measured by the Cockroft-Gault formula
• Able to start study treatment within 90 days of completion of chemoradiation.

You may not qualify if:

• Evidence of distant metastases or lymph node metastasis (es) that was not within the radiation field.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. A history of localized early stage malignancy that has undergone potentially curative therapy or is low grade and does not require active treatment is allowed.
• Diffuse bladder carcinoma in situ (CIS) that was not able to be encompassed in a boost radiotherapy volume
• Patients with inflammatory bowel disease
• Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration. Inhaled, ocular, intraarticular, intranasal and topical steroids are permitted.
• Patients with a known chronic immunocompromised state, HIV infection or active Hepatitis B or Hepatitis C infection.
• Pregnancy or women of childbearing potential not willing to use contraception and men who are sexually active and not willing/able to use medically acceptable forms of contraception and breast-feeding women not willing to stop breastfeeding during study.
• Severe active co-morbidity as determined by the investigator or principal investigator
• Life expectancy less than 2 years

Sponsors & Collaborators

• Bristol-Myers Squibb: collaborator
• University of Utah: lead

Study Sites (2)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Galarza Fortuna GM, Grass D, Maughan BL, Jain RK, Dechet C, Beck J, Schuetz E, Sanchez A, O'Neil B, Poch M, Li R, Lloyd S, Tward J, Phunrab T, Hawks JL, Swami U, Boucher KM, Agarwal N, Gupta S. Nivolumab adjuvant to chemo-radiation in localized muscle-invasive urothelial cancer: primary analysis of a multicenter, single-arm, phase II, investigator-initiated trial (NEXT). J Immunother Cancer. 2025 Mar 18;13(3):e010572. doi: 10.1136/jitc-2024-010572.

  PMID: 40102029 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 2, single arm, open label trial

Study Record Dates

• First Submitted: May 25, 2017
• First Posted: May 31, 2017
• Study Start: July 10, 2017
• Primary Completion: February 10, 2025
• Study Completion (Estimated): October 31, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)