Trial Search Results

Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

This phase II trial studies how well atezolizumab works in treating patients with non-muscle invasive bladder cancer that has come back and has not responded to treatment with Bacillus Calmette-Guerin (BCG). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: Atezolizumab
  • Other: Laboratory Biomarker Analysis

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Patients must have histologically proven, recurrent, non-muscle invasive urothelial
   carcinoma of the bladder within 60 days prior to registration; the carcinoma must be
   stage T1 high-grade, stage CIS, or stage Ta high-grade

   - Patients with mixed urothelial carcinoma and a glandular and/or squamous component
   will be eligible for the trial, but the presence of other histologic variants, pure
   adenocarcinoma, or pure squamous cell carcinoma, will make a patient ineligible

   - Patients must have had all visible tumor resected completely within 60 days prior to
   registration; CIS disease is not expected to be completely excised; all patients must
   have tumor tissue from the histologic diagnosis of recurrence available for central
   pathology review submission; failure to submit these materials will make the patient
   ineligible for this study

   - Patients must have had cystoscopy confirming no visible papillary tumor within 21 days
   prior to registration; (CIS disease is not expected to have been completely excised)

   - Patients must have had cytology within 21 days prior to registration; cytology for
   patients with CIS component is not expected to be negative for malignant cells; if the
   cytology for patients with only Ta/T1 disease is positive for malignant cells, patient
   must have had a biopsy of the prostatic urethra within the previous six months

   - All patients with T1 urothelial carcinoma must undergo re-transurethral resection of
   bladder tumor (TURBT) within 60 days prior to registration, and must have uninvolved
   muscularis propria in the pathologic specimen from either the first or the second
   TURBT; tissue from the re-resection must be submitted; the TURBT that identified the
   recurrent T1 disease may have taken place more than 60 days prior to registration

   - Patients must not have had urothelial carcinoma in the prostate or upper urinary tract
   within the previous 24 months, or muscle invasive urothelial carcinoma of the bladder
   at any time; patients must have a computed tomography (CT) or magnetic resonance
   imaging (MRI) of the abdomen and pelvis to rule out upper tract malignancy and
   intra-abdominal metastases within 90 days prior to registration

   - Patients must be deemed unfit for radical cystectomy by the treating physician, or the
   patient must refuse radical cystectomy, which is considered standard of care for these
   patients; the reason for patients not to undergo cystectomy will be clearly documented

   - Patients must be BCG-unresponsive; a patient is BCG-unresponsive if they meet one or
   more of the following criteria:

      - Patient has persistent or recurrent high-grade Ta/CIS urothelial carcinoma after
      completing therapy with at least induction BCG (>= 5 doses) and first round
      maintenance or second induction BCG (>= 2 doses)

      - Patient has high grade T1 urothelial carcinoma after induction BCG (>= 5 doses)
      only or after induction BCG (>= 5 doses) and first round maintenance or second
      induction BCG (>= 2 doses)

      - Patient is disease-free at 6 months after starting BCG (i.e., complete response)
      but then experiences a high-grade recurrence within 6 months after the last BCG
      dose

   - All adverse events associated with any prior surgery and intravesical therapy must
   have resolved to grade =< 2 prior to registration

   - Patients must not have had systemic chemotherapy or immunotherapy, including, but not
   limited to interferon alfa-2b, high dose interleukin 2 (IL-2), pegylated interferon
   (PEG-IFN), PD-1, anti-PD-L1, intra-tumoral, or vaccine therapies within 6 weeks prior
   to cycle 1, day 1; patients must not have received or be planning to receive any of
   the prohibited therapies during protocol treatment; prior intravesical interferon
   therapy is allowed

   - Patients must not be planning to receive concomitant other biologic therapy, radiation
   therapy, intravesical chemotherapy, surgery, or other therapy while on this protocol

   - Patients must not have received any prior radiation to the bladder for bladder cancer

   - Patients must not have received treatment with systemic immunosuppressive medications
   (including, but not limited to, prednisone, cyclophosphamide, azathioprine,
   methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 4
   weeks prior to cycle 1, day 1; exceptions: (1) patients may have received acute, low
   dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone
   for nausea); (2) the use of inhaled corticosteroids and mineralocorticoids (e.g.,
   fludrocortisone) for patients with orthostatic hypotension or adrenocortical
   insufficiency is allowed

   - Patients must not have received of a live, attenuated vaccine within 4 weeks before
   cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required
   during the study and up to 5 months after the last dose of atezolizumab

      - Influenza vaccination should be given during influenza season only (approximately
      October to March); patients must not receive live, attenuated influenza vaccine
      within 4 weeks prior to cycle 1, day 1 or at any time during the study

   - Patients must not require treatment with a RANKL inhibitor (e.g. denosumab) who cannot
   discontinue it before treatment with atezolizumab

   - Absolute neutrophil count (ANC) >= 1,500 microliter (mcL) (within 42 days prior to
   registration)

   - Platelets >= 100,000/mcL (within 42 days prior to registration)

   - Hemoglobin >= 9 g/dL (within 42 days prior to registration)

   - Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's
   syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 42 days prior to
   registration)

   - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2 x IULN (within
   42 days prior to registration)

   - Alkaline phosphatase =< 2 x IULN (within 42 days prior to registration)

   - Serum creatinine =< 1.5 ULN OR measured or calculated creatinine clearance >= 30
   mL/min (within 42 days prior to registration)

   - Patients must have Zubrod performance status =< 2

   - Patients must have a baseline electrocardiograph (ECG) performed within 42 days prior
   to registration

   - Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including
   drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
   organizing pneumonia, etc.), or evidence of active pneumonitis

   - Patients must not have an active infection requiring oral or IV antibiotics within 14
   days prior to registration; patients receiving prophylactic antibiotics (e.g., for
   prevention of a urinary tract infection or chronic obstructive pulmonary disease) are
   eligible

   - Patients must not have severe infections within 28 days prior to registration,
   including but not limited to hospitalization for complications of infection,
   bacteremia, or severe pneumonia

   - Patients must not have active autoimmune disease that has required systemic treatment
   in past two years (i.e., with use of disease modifying agents, corticosteroids or
   immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment; autoimmune diseases include, but
   are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory
   bowel disease, vascular thrombosis associated with antiphospholipid syndrome,
   Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome,
   multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis

   - Patients must not have undergone prior allogeneic bone marrow transplantation or prior
   solid organ transplantation

   - Patient must not have active tuberculosis

   - Patients must not have active hepatitis B (chronic or acute) or active hepatitis C
   infection

      - Patients with past or resolved hepatitis B infection (defined as having a
      negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
      [antibody to hepatitis B core antigen] antibody test) are eligible

      - Patients positive for hepatitis C virus (HCV) antibody are eligible only if
      polymerase chain reaction (PCR) is negative for HCV RNA

   - Patients positive for human immunodeficiency virus (HIV) are eligible only if they
   have all of the following:

      - A stable regimen of highly active anti-retroviral therapy (HAART)

      - No requirement for concurrent antibiotics or antifungal agents for the prevention
      of opportunistic infections

      - A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard
      PCR-based tests

   - No other prior malignancy is allowed except, for the following: adequately treated
   basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
   stage I or II cancer from which the patient is currently in complete remission, or any
   other cancer from which the patient has been disease free for five years

   - Patients must not be pregnant or nursing due to the potential teratogenic side effects
   of the protocol treatment; administration of atezolizumab may have an adverse effect
   on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of
   child-bearing potential and men must agree to use adequate contraception (hormonal or
   barrier method of birth control; abstinence) prior to study entry, for the duration of
   study participation, and for 5 months (150 days) after the last dose of study agent; a
   woman is considered to be of "reproductive potential" if she has had menses at any
   time in the preceding 12 consecutive months; should a woman become pregnant or suspect
   she is pregnant while she or her partner is participating in this study, she should
   inform her treating physician immediately

   - Due to the potential drug reaction with atezolizumab, patients must not be known to be
   allergic to Chinese hamster egg or ovaries

   - Patients must be offered the opportunity to participate in specimen banking for future
   studies, to include translational medicine studies

   - Patients must be informed of the investigational nature of this study and must sign
   and give written informed consent in accordance with institutional and federal
   guidelines

   - As a part of the oncology patient enrollment network (OPEN) registration process the
   treating institution's identity is provided in order to ensure that the current
   (within 365 days) date of institutional review board approval for this study has been
   entered in the system

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Brittany Lim
650-725-1202
Recruiting