Nivolumab in Treating Patients with Stage II-IV Muscle-Invasive Bladder, Urethra, or Ureter Cancer That Have Undergone Chemoradiotherapy

Status: Active

Description

This phase II trial studies how well nivolumab works in treating patients with stage II-IV muscle-invasive bladder, urethra, or ureter cancer that have undergone chemoradiotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Eligibility Criteria

Inclusion Criteria

  • PRE-CHEMORADIATION SAMPLE COLLECTION: 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; 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
  • PRE-CHEMORADIATION SAMPLE COLLECTION: Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: Platinum-based chemotherapy prior to chemoradiation is permitted but not mandatory
  • STUDY TREATMENT: Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • STUDY TREATMENT: White blood cells (WBC) >= 2000/ul
  • STUDY TREATMENT: Neutrophils >= 1500/ul
  • STUDY TREATMENT: Hemoglobin >= 9.0 g/dl
  • STUDY TREATMENT: Serum bilirubin value less than 1.5 times the upper limit of the normal range
  • STUDY TREATMENT: Serum aminotransferase value less than 1.5 times the upper limit of the normal range
  • STUDY TREATMENT: Creatinine clearance of 20 ml/min or greater as measured by the Cockcroft-Gault formula
  • STUDY TREATMENT: Able to start study treatment in less than or equal to 90 days after completion of chemoradiation
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: 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
  • STUDY TREATMENT: All toxicities attributed to prior anti-cancer therapy other than nephropathy, neuropathy, hearing loss, alopecia and fatigue must have resolved to grade 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [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
  • STUDY TREATMENT: 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, human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection
  • Pregnant women, women of childbearing potential not willing to use contraception, 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 the study
  • Severe active co-morbidity as determined by the investigator or principal investigator
  • Life expectancy less than 2 years

Locations & Contacts

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Sumati Virendra Gupta
Phone: 801-213-5727
Email: sumati.gupta@hci.utah.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the two-year rate of failure-free survival (FFS).

SECONDARY OBJECTIVES:

I. Evaluate the rate of failure-free survival at two years in subjects with intact bladder (FFSIB).

II. Evaluate the rate of acute and late grade 2 or higher treatment-related genitourinary (GU), gastrointestinal (GI), hematologic, and immune related toxicity.

III. Evaluate the effect of treatment on quality of life.

IV. Evaluate cystoscopic local control at 6 months, 1 year and 2 years post start of chemoradiation after censoring for distant recurrence.

V. Evaluate the rate of salvage cystectomy.

VI. Evaluate the rate of distant failure-free survival at two years in subjects with intact bladder and those that undergo salvage cystectomy.

VII. Evaluate overall survival up to 5 years.

EXPLORATORY OBJECTIVES:

I. To asses immunological monitoring on peripheral blood mononuclear cells and other humoral factors collected prior to the initiation of chemoradiation, study therapy, and throughout the study drug administration.

II. To characterize changes in immune cell and immune factor subsets that can be correlated with clinical outcome.

III. To assess the correlation of response to PD-L1 expression in pretreatment tumor tissue in the study subjects.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years, semi-annually for 1 year, and annually for 2 years or every 3 months for 3 years and then every 6 months for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Huntsman Cancer Institute / University of Utah

Principal Investigator
Sumati Virendra Gupta

Trial IDs

Primary ID HCI100769
Secondary IDs NCI-2017-01197, CA209-999, NEXT
Clinicaltrials.gov ID NCT03171025