A Study of Risk Enabled Therapy After Neoadjuvant Immunochemotherapy for Bladder Cancer

NCT04506554 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: GU-17620-1047
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 4

Brief Summary

Neoadjuvant accelerated methotrexate/vinblastine/adriamycin/cisplatin (AMVAC) in combination with nivolumab is under evaluation for the treatment of muscle invasive bladder cancer (MIBC). Patients with pre-specified tumor mutations and complete clinical response with neoadjuvant therapy will preserve their bladders and go on active surveillance.

Conditions

Muscle-Invasive Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Metastasis-free survival (MFS)

  MFS is defined as a recurrence of urothelial carcinoma that is \>cN1 (more than one clinically suspicious pelvic lymph node) or surgically unresectable local recurrence (e.g., \>cT4a) or M1 disease.

  2 years

Secondary Outcomes (3)

• Number of days of Overall survival

  up to 5 years

• Number of days of Progression free survival

  up to 5 years

• Number of patients erporting Toxicity of neoadjuvant nivolumab and AMVAC therapy

  until 100 days after the last nivolumab/AMVAC

Study Arms (1)

AMVAC + nivolumab

EXPERIMENTAL

This will be a single-arm, open-label, multicenter phase 2 study of neoadjuvant nivolumab with AMVAC. Approximately 70 evaluable patients will be enrolled into this study. Eligible patients will be those with diagnosis of muscle invasive urothelial carcinoma of the bladder who are cT2 or cT3 but not clinical N1 at diagnosis. Clinical stage is confirmed by transurethral resection of bladder tumor (TURBT#1).

Drug: AMVAC + Nivolumab

Interventions

AMVAC + Nivolumab DRUG

Nivolumab 240mg will be administered intravenously for 3 doses - on days 1, 15 and 29. AMVAC will be dosed intravenously every 2 weeks for 3 doses on days 1, 15 and 29 with Neulasta or equivalent. Standard AMVAC dose is as follows: methotrexate 30mg/m2, vinblastine 3mg/m2, doxorubicin 30mg/m2, and cisplatin 70mg/m2.

AMVAC + nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 years
• Primary urothelial or predominantly urothelial carcinoma of the bladder confirmed from pathology report. Patients with some component of variant histology mixed with predominant urothelial carcinoma will be allowed. Upper tract urothelial carcinoma patients are not allowed.
• Urothelial carcinoma of the prostatic urethra in men is allowed
• Histologic evidence of muscularis propria invasion.
• AJCC23 clinical stage T2-T3 N0M0.
• No radiographic evidence of lymph node positive disease as per RECIST 1.1 (≥15 mm short axis diameter). Lymph node positive disease is defined as clinical lymphadenopathy on staging CT or MRI greater than 1.4 cm in the short axis. If a lymph node is greater than 1.4 cm, it has to be biopsy proven negative for the patient to be eligible.
• No metastatic disease (M0).
• ECOG performance status 0, or 1.
• Left ventricular ejection fraction ≥ 50% by MUGA or ECHO within 6 months of study entry.
• Negative pregnancy test in women of child bearing potential within 24 hours of study registration. If the pregnancy test is positive, the patient must not receive protocol treatment and must not be enrolled in the study.
• Normal organ and bone marrow function (Leukocytes ≥ 3,000/mcL, Absolute neutrophil count ≥ 1,500/mcL, Platelets ≥ 100,000/mcL, Total bilirubin ≤ institutional upper limit of normal (ULN) unless patient has known Gilbert's disease, in which case an elevated bilirubin is allowed, AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN, Creatinine Clearance ≥ 50 mL/min calculated using the Cockroft-Gault formula or measured with 24 hour urine collection)

You may not qualify if:

• Any component of small cell histology.
• Prior systemic chemotherapy or radiation therapy for urothelial carcinoma or cytotoxic chemotherapy for another malignancy within 1 year of study entry are ineligible. Patients who received immunotherapy for non-muscle invasive bladder cancer will be excluded
• Has a known additional malignancy that has had progression or has required active treatments in the last three years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with surgery is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; PSA undetectable for 1 year while off androgen deprivation therapy. Patients on active surveillance for low grade prostate cancer are allowed to participate.
• Patients who have received experimental agents within 4 weeks of study entry.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Methotrexate, Vinblastine, Doxorubicin or Cisplatin or other agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined by current oral or intravenous antibiotic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects of cytotoxic chemotherapy.
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Patients with hydronephrosis that has not been addressed with a documented assessment (i.e. normal GFR, no intervention necessary) or an intervention such as placement of a stent or nephrostomy tube.
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease. Use of steroids as pre-medication for contrast allergy prior to CT scans is permitted. It is acceptable to use steroids as pre-medication for AMVAC.
• History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Prior treatment with CD137 agonists, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (4)

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pooja Ghatalia, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: August 10, 2020
• Study Start: December 1, 2020
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (4)