Clinical Trials /

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

NCT03171025

Description:

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.

Related Conditions:
  • Bladder Adenocarcinoma
  • Bladder Carcinoma
  • Bladder Squamous Cell Carcinoma
  • Transitional Cell Carcinoma
  • Ureter Adenocarcinoma
  • Ureter Squamous Cell Carcinoma
  • Urethral Adenocarcinoma
  • Urethral Carcinoma
  • Urethral Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer
  • Official Title: A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)

Clinical Trial IDs

  • ORG STUDY ID: HCI100769
  • NCT ID: NCT03171025

Conditions

  • Bladder Cancer

Interventions

DrugSynonymsArms
NivolumabNivolumab, all patients

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab, all patientsExperimental
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4a, 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.

               -  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 must have histologically proven primary carcinoma of the bladder or urethra
             or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)

          -  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.

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 5 months after the last dose of study medication. Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 7 months after the last dose of study therapy.

          -  All toxicities attributed to prior anti-cancer therapy other than nephropathy,
             neuropathy, hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI
             CTCAE version 4.03) or baseline before administration of study drug. Subjects with
             toxicities attributed to prior anti-cancer therapy which are not expected to resolve
             and result in long lasting sequelae, such as neuropathy after platinum based therapy,
             are permitted to enroll.

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Two-year rate of failure-free survival (FFS)
Time Frame:2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Rate of failure-free survival at two years in subjects with intact bladder (FFSIB).
Time Frame:2 years
Safety Issue:
Description:This will be measured only in subjects who do not have local recurrence requiring radical cystectomy. The endpoint of FFSIB 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.
Measure:Rate of acute and late grade 2 or higher treatment related Genitourinary, Gastrointestinal, hematologic and immune related adverse events.
Time Frame: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)
Safety Issue:
Description:
Measure:Effect of treatment on Quality of Life
Time Frame:Quality of life questionnaires done every 3 months while patients are on treatment for 1 year
Safety Issue:
Description:
Measure:Cystoscopic Local Control
Time Frame:Done at 6 months, 1 year and 2 years
Safety Issue:
Description:Evaluate cystoscopic local control at 6 months, 1 year and 2 years post start of chemoradiation after censoring for distant recurrence. The endpoint will be measurement of local recurrence at 6 months, 1 year and 2 years as determined by cystoscopy.
Measure:Rate of salvage cystectomy
Time Frame:During study treatment that is expected to last for 1 year
Safety Issue:
Description:Evaluate the rate of salvage cystectomy. This will be measured by the endpoint of radical cystectomy for local recurrence during study treatment.
Measure:Rate of distant failure free survival
Time Frame:2 years
Safety Issue:
Description:Evaluate the rate of distant failure free survival at two years in subjects with intact bladder and those who discontinue study to undergo salvage cystectomy. This will be measured in subjects who do and do not have local recurrence requiring radical cystectomy during study treatment. The endpoint FFS will be determined based on disease recurrence date defined as the time between the start date of chemoradiation and the date of first distant recurrence or non-cancer related death.
Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description:Evaluate overall survival up to 5 years. This will be measured by the rate of death for up to 5 years from start of chemoradiation

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Trial Keywords

  • Muscle Invasive

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