A Study to Test the Safety of Immunotherapy With Nivolumab Alone or With Ipilimumab Before Surgery for Bladder Cancer Patients Who Are Not Suitable for Chemotherapy

Conditions:Cancer, Cancer, Bladder Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:April 25, 2018
End Date:January 2021
Contact:Min Yuen Teo, MB BCh

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A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)

The purpose of this study is to test if immunotherapy with nivolumab alone or in combination
with ipilimumab is safe and does not delay the planned bladder cancer surgery. The
investigators want to see if treatment with these drugs prior to surgery may decrease the
size of the bladder cancer and thus could help make the surgery more successful.

Inclusion Criteria:

- Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant
histology is acceptable if there is a predominant urothelial component.

- Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with
cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of
muscle invasion are eligible.

- Patients ineligible for cisplatin based on any of the following criteria:

- Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min

- Grade 2 or above audiometric hearing loss (per CTCAE v4.0)

- Grade 2 or above peripheral neuropathy (per CTCAE v4.0)

- Availability of tumor specimen block or 30 unstained slides from diagnosis of
muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled
after discussion with the Principal Investigator.

- Karnofsky performance status ≥ 70%.

- Age ≥ 18 years.

- Required initial laboratory values:

- Absolute neutrophil count ≥ 1.5 x 10^9/L

- Platelets ≥ 100 x 10^9/L

- Bilirubin ≤1.5 times the upper limit of normal (x ULN)

- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN

- PTT/PT ≤1.5 x ULN or INR < 1.7 x ULN for patients who are not receiving
therapeutic anticoagulation. Patients receiving therapeutic anticoagulation
should be on a stable dose.

Exclusion Criteria:

- Prior treatment with systemic chemotherapy for bladder cancer. (Prior intravesical
treatment is allowed.)

- Prior bladder-directed radiotherapy.

- Presence of active autoimmune disease, symptoms, or conditions, with the following

°Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune thyroiditis only requiring hormone replacement, asymptomatic laboratory
evidence of autoimmune disease (e.g.: +ANA, +RF, anti-thyroglobulin antibodies), or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.

- Subjects with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement
steroid doses are permitted in the absence of active autoimmune disease.

- Unstable angina.

- New York Heart Association (NYHA) Grade II or greater congestive heart failure.

- History of myocardial infarction within 6 months.

- History of stroke within 6 months.

- Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is
permitted, but patients must be on a stable dose.

- Major surgical procedure within 28 days prior to the study.

- Serious, non-healing wound, ulcer, or bone fracture.

- Other prior malignancy active within the previous 2 years except for local or
organ-confined early stage cancer that has been definitively treated with curative
intent or does not require treatment, does not require ongoing treatment, has no
evidence of active disease, and has a negligible risk of recurrence and is therefore
unlikely to interfere with the endpoints of the study.

- Subjects who have received prior therapy with any T cell co-stimulation or checkpoint
pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other
medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.

- Prior therapy with intravesical BCG within 6 weeks of treatment.

- Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or
positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
antibody test indicating acute or chronic infection.

- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).

- History of allergy to study drug component or history of severe hypersensitivity
reaction to any monoclonal antibody.

- Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test
within 14 days of first dose.

- Male subjects who are unwilling to use contraception during the treatment and for at
least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus
90 days duration of sperm turnover).

- Women of childbearing potential (WOCBP) not using a medically acceptable means of
contraception throughout the study treatment and for at least 23 weeks following the
last dose of study treatment (5 half-lives of study drug plus 30 days duration of
ovulatory cycle).

- WOCBP are defined as those who have experienced menarche and who have not
undergone successful surgical sterilization (hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopausal
is defined as:

- Amenorrhea ≥ 12 consecutive months without another cause, or

- For women with irregular menstrual periods and on hormone replacement therapy
(HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness.

- Inability to comply with study and/or follow-up procedures.
We found this trial at
500 Westchester Avenue
Harrison, New York 10604
Phone: 914-367-7393
Harrison, NY
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136 Mountainview Boulevard
Basking Ridge, New Jersey 07920
Phone: 914-367-7393
Basking Ridge, NJ
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1275 York Ave
New York, New York 10021
(212) 639-2000
Phone: 914-367-7393
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
New York, NY
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