ACTIVE_NOT_RECRUITING

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

Bladder Cancer Immunotherapy Nivolumab Ipilimumab 18-042

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2018-04-25

Study Completion:2026-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT03520491

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component. * For MUSCLE-INVASIVE UROTHELIAL CANCER OF THE BLADDER (Cohorts 1 - 3): * For UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT (URETER OR RENAL PELVIS) (Cohort U): * 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%. * Medically appropriate candidate for radical cystectomy, as per MSK Attending Urologic Oncologist * 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.	* Prior treatment with systemic chemotherapy for urothelial cancer, including immune checkpoint inhibitors for non-muscle invasive bladder cancer. (Prior intravesical treatment such as BCG is allowed.) * Prior bladder-directed radiotherapy (exclusion applies only to MIBC Cohorts 1 - 3). * Presence of active autoimmune disease, symptoms, or conditions, with the following exceptions: * 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. (Transurethral resection of bladder tumor is permitted * 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.

Inclusion Criteria

Exclusion Criteria

* Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
* For MUSCLE-INVASIVE UROTHELIAL CANCER OF THE BLADDER (Cohorts 1 - 3):
* For UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT (URETER OR RENAL PELVIS) (Cohort U):
* 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%.
* Medically appropriate candidate for radical cystectomy, as per MSK Attending Urologic Oncologist
* 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.

* Prior treatment with systemic chemotherapy for urothelial cancer, including immune checkpoint inhibitors for non-muscle invasive bladder cancer. (Prior intravesical treatment such as BCG is allowed.)
* Prior bladder-directed radiotherapy (exclusion applies only to MIBC Cohorts 1 - 3).
* Presence of active autoimmune disease, symptoms, or conditions, with the following exceptions:
* 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. (Transurethral resection of bladder tumor is permitted
* 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.

Contacts and Locations

Principal Investigator

Scott Niglio, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Commack (All protocol activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (All protocol activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Scott Niglio, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-04-25

Study Completion Date2026-01

Study Record Updates

Study Start Date2018-04-25

Study Completion Date2026-01

Terms related to this study

Keywords Provided by Researchers

Immunotherapy
Nivolumab
Ipilimumab
18-042

Additional Relevant MeSH Terms

Bladder Cancer