Recruiting PHASE2, PHASE3 Muscle Invasive Bladder Urothelial Carcinoma

New treatment option for Muscle Invasive Bladder Urothelial Carcinoma

Official title Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study

ClinicalTrials.gov ID: NCT05987241

What this study is testing

What is Nivolumab?

Nivolumab is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for muscle invasive bladder urothelial carcinoma.

Also referred to as ABP 206, BCD-263.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing
This phase II/III trial examines whether patients who have undergone surgical removal of bladder, kidney, ureter or urethra, but require an additional treatment called immunotherapy to help prevent their urinary tract (urothelial) cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans.
  • Phase 3: a large, late-stage study
  • Which group you join is decided by chance.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

  • PRE-REGISTRATION (STEP 0): Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter or renal pelvis
  • PRE-REGISTRATION (STEP 0): Variant histology, including neuroendocrine differentiation, sarcomatoid, micropapillary, glandular, trophoblastic...
  • PRE-REGISTRATION (STEP 0): Radical surgery (cystectomy with lymph node dissection or nephroureterectomy or ureterectomy) must be ≥ 3 weeks and ≤ 12...
  • PRE-REGISTRATION (STEP 0): Patients who have had a partial cystectomy as definitive therapy are not eligible
  • PRE-REGISTRATION (STEP 0): No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e...
See the full eligibility criteria
Who can join
  • PRE-REGISTRATION (STEP 0): Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter or renal pelvis
  • PRE-REGISTRATION (STEP 0): Variant histology, including neuroendocrine differentiation, sarcomatoid, micropapillary, glandular, trophoblastic, Mullerian, is allowed if urothelial cancer is predominant histology (any...
  • PRE-REGISTRATION (STEP 0): Radical surgery (cystectomy with lymph node dissection or nephroureterectomy or ureterectomy) must be ≥ 3 weeks and ≤ 12 weeks (central Signatera pathway) or ≤ 16 weeks (commercial Signatera...
  • PRE-REGISTRATION (STEP 0): Patients who have had a partial cystectomy as definitive therapy are not eligible
  • PRE-REGISTRATION (STEP 0): No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e., "positive margins") are allowed. Carcinoma in situ (CIS) at margins is...
  • PRE-REGISTRATION (STEP 0): No evidence of residual cancer or metastasis after radical cystectomy or nephroureterectomy or ureterectomy (imaging is not required prior to pre-registration but is required prior to...
  • PRE-REGISTRATION (STEP 0): Have undergone a radical cystectomy nephroureterectomy, or ureterectomy with pathological evidence of urothelial carcinoma at high risk of recurrence as described in one of the two scenarios...
  • (i) Patients who have not received neoadjuvant systemic therapy: pT4N0 or pTanyN+ on radical surgery pathology specimen (i.e., cystectomy, nephroureterectomy, or ureterectomy) and are not eligible for adjuvant cisplatin...
  • (i) Patients ineligible for cisplatin due to at least one of the following criteria and reason for ineligibility should be documented:
  • (i) Creatinine Clearance (using Cockcroft-Gault): \< 60 mL/min
  • (i) Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade \>= 2 audiometric hearing loss
  • (i) CTCAE version 5, grade \>= 2 or above peripheral neuropathy
  • New York Heart Association Class III heart failure
  • (i) Eastern Cooperative Oncology Group (ECOG) performance status = 2
  • (i) Patients who are eligible for adjuvant cisplatin may be candidates if they refuse adjuvant cisplatin-based chemotherapy, despite being informed by the investigator about the treatment options. The patient's refusal...
  • (i) Patients with pT2N0 urothelial cancer on radical surgery specimen (without prior neoadjuvant systemic therapy) with ctDNA(+) Signatera results are eligible only if the result was obtained via commercial testing...
  • (ii) Patients who received neoadjuvant systemic therapy: ypT2-T4N0 or Nx or ypTanyN+ on radical surgery (i.e., cystectomy. , nephroureterectomy, or ureterectomy) pathology specimen. Neoadjuvant systemic therapy may have...
  • PRE-REGISTRATION (STEP 0): Patients are required to meet criteria for one of two criteria:
  • 1) Commercial Signatera pathway:
  • Available commercial Signatera testing result (i.e., ctDNA+ or ctDNA-) from blood sample obtained ≥ 3 weeks and ≤ 16 weeks from time of radical surgery performed as part of standard care
  • Sites are required to verify that the commercial Signatera report demonstrates a complete 16 target assay design and that the test was designed on exome. This verification is conducted at the site level during the...
  • Central Signatera pathway:
  • Pre-registration samples are to be submitted after pre-registration, at ≥ 3 weeks but ≤ 12 weeks from the time of radical surgery
  • Ineligible patients for the commercial pathway must use the central Signatera pathway and provide tumor tissue as part of the A032103 study
  • For patients who have not had neoadjuvant chemotherapy, tumor tissue is preferred from the radical surgery specimen
  • For patients who have had neoadjuvant therapy, tissue is preferred from the pre-chemotherapy specimen diagnosing muscle-invasive disease (e.g., transurethral resection of bladder tumor specimen)
  • PRE-REGISTRATION (STEP 0): Age \>= 18 years
  • PRE-REGISTRATION (STEP 0): ECOG performance status 0-2
  • PRE-REGISTRATION (STEP 0): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
  • PRE-REGISTRATION (STEP 0): No postoperative adjuvant systemic therapy after radical surgery
  • PRE-REGISTRATION (STEP 0): No adjuvant radiation after radical surgery
  • PRE-REGISTRATION (STEP 0): No treatment with any other type of investigational agent =\< 4 weeks before pre-registration
  • PRE-REGISTRATION (STEP 0): No previous treatment with LAG-3 blockade therapy
  • PRE-REGISTRATION (STEP 0): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the...
  • PRE-REGISTRATION (STEP 0): Absolute neutrophil count (ANC) \>= 1,200/mm\^3
  • PRE-REGISTRATION (STEP 0): Platelet count \>= 100,000/mm\^3
  • PRE-REGISTRATION (STEP 0): Hemoglobin \>= 8 g/dL
  • PRE-REGISTRATION (STEP 0): Creatinine =\ 30 mL/min (using either Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • PRE-REGISTRATION (STEP 0): Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN
  • PRE-REGISTRATION (STEP 0): Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
  • PRE-REGISTRATION (STEP 0): For women of childbearing potential only: A negative urine or serum pregnancy test done =\< 14 days prior to pre-registration is required
  • PRE-REGISTRATION (STEP 0): Not currently requiring hemodialysis
  • PRE-REGISTRATION (STEP 0): No current or prior history of myocarditis
  • PRE-REGISTRATION (STEP 0): No history of a grade ≥ 3 immune related adverse event with prior PD-1/PD-L1 blockade in the neoadjuvant setting
  • PRE-REGISTRATION (STEP 0): No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic...
  • PRE-REGISTRATION (STEP 0): Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
  • PRE-REGISTRATION (STEP 0): Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear...
  • PRE-REGISTRATION (STEP 0): No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years.
  • PRE-REGISTRATION (STEP 0): No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
  • PRE-REGISTRATION (STEP 0): For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C...
  • PRE-REGISTRATION (STEP 0): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
  • PRE-REGISTRATION (STEP 0): No concurrent antineoplastic therapy including anti-hormonal treatments used for cancer therapy (e.g., leuprolide, antiandrogens)
  • PRE-REGISTRATION (STEP 0): No current immunosuppressive agents (except for corticosteroids as described below).
  • PRE-REGISTRATION (STEP 0): No condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of pre-registration (with...
  • REGISTRATION (STEP 1): Patient must have had radical cystectomy and lymph node dissection or nephroureterectomy or ureterectomy =\< 18 weeks prior to registration.
  • REGISTRATION (STEP 1): Must have evaluable ctDNA Signatera assay result (i.e., ctDNA+ or ctDNA-) based on either:
  • Commercial Signatera result OR
  • Central Signatera testing result (i.e. testing that was performed as part of A032103.)
  • REGISTRATION (STEP 1): All patients must have confirmed disease-free status defined as no measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or definitive non-measurable radiographic...
  • REGISTRATION (STEP 1): No major surgery =\< 3 weeks before registration.
  • REGISTRATION (STEP 1): No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow...
  • REGISTRATION (STEP 1): No change since Step 0 pre-registration in clinical condition and/or laboratory tests that would impact the safety of nivolumab +/- relatlimab administration in the opinion of the treating...
  • REGISTRATION (STEP 1): No evidence of high grade urothelial cancer in the bladder for patients with primary urothelial cancers of the upper urinary tract
  • RE-REGISTRATION (STEP 2) COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
  • Patient must have converted to ctDNA(+) during serial monitoring performed centrally as part of A032103
  • RE-REGISTRATION (STEP 2) COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
  • No evidence of metastatic disease on the most recent scheduled imaging assessment as outlined in the study calendar (no repeat imaging is necessary specifically at the time of the conversion from ctDNA[-] to ctDNA[+]).
  • RE-REGISTRATION (STEP 2) COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
  • In the opinion of the treating investigator, patient clinical condition and laboratory tests would not impact the safety of nivolumab administration in the opinion of the treating investigator

The study team makes the final eligibility decision.

Where it's taking place

  • Phoenix, Arizona, United States
  • Tucson, Arizona, United States
  • Fayetteville, Arkansas, United States
  • Rogers, Arkansas, United States
  • Springdale, Arkansas, United States
  • Anaheim, California, United States
  • Baldwin Park, California, United States
  • Bellflower, California, United States
  • Dublin, California, United States
  • Fontana, California, United States
  • Fremont, California, United States
  • Fresno, California, United States
  • Harbor City, California, United States
  • Irvine, California, United States
  • La Jolla, California, United States
  • Los Angeles, California, United States
  • Modesto, California, United States
  • Newport Beach, California, United States
  • Oakland, California, United States
  • Ontario, California, United States

+ 361 more site(s).

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Phoenix, Arizona, United States; Tucson, Arizona, United States; Fayetteville, Arkansas, United States; Rogers, Arkansas, United States; Springdale, Arkansas, United States; Anaheim, California, United States and 375 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.