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Stage II Bladder Urothelial Carcinoma AJCC v6 and v7Phase 2NCT03421652

Nivolumab and RT in Treating Patients With Localized/Locally Advanced Urothelial Bladder Cancer Ineligible for Chemo

A Phase 2 study testing Nivolumab and Radiation in people with Stage II Bladder Urothelial Carcinoma AJCC v6 and v7 and Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, run by Barbara Ann Karmanos Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well nivolumab works with radiation therapy in treating patients with urothelial bladder cancer that has spread from its original site of growth to nearby tissues or lymph nodes and are ineligible for chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesUnited States
Study dates
24 Apr 2018to 23 Mar 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Localized urothelial cancer of bladder with presence of transitional cell carcinoma (TCC) component; mixed histologies are allowed Clinical or pathologic stage T2 -T4 disease including T4a and 4b if feasible to treat with radiation therapy Locoregional lymph node metastases are permitted but patients with distant metastases are ineligible; imaging to evaluate for distant metastases should consist of a minimum of computed tomography (CT)/magnetic resonance imaging (MRI) of abdomen/pelvis or CT urogram and a chest x-ray (CXR) or CT chest; patients for which there is clinical suspicion or symptoms of bone metastasis should have a bone scan completed to rule out metastatic disease prior to enrollment on study Agreeable to consider radiation therapy (RT) for the urothelial cancer: patients have to be evaluated by a radiation oncologist and deemed to be candidates for RT
  • The patients must not be candidates for chemotherapy due to at least one of the following reasons:
  • Performance status of 2
  • Creatinine clearance =< 60 ml/min as calculated by the Cockcroft-Gault formula
  • Cardiac disease such as New York Heart Association (NYHA) class III or IV heart failure or cardiac ischemia within the last 12 months, grade 2 or greater neuropathy, or other comorbidities based on which patient is not considered a candidate for chemotherapy Alkaline phosphatase =< 3 x upper limit of normal Aspartate aminotransferase (AST) =< 3 x upper limit of normal Alanine aminotransferase (ALT) =< 3 x upper limit of normal Bilirubin < 1.5 x upper limit of normal (ULN) Absolute neutrophil count >= 1500/mm^3 Hemoglobin >= 9 g/dL Platelets >= 100 K/mm^3 Performance score (PS) of 0-2 by Zubrod score Life expectancy of 12 months Willingness to sign informed consent Patients cannot have active autoimmune disease or immunosuppressive conditions Serum creatinine =< 1.5 X institutional ULN or creatinine clearance > 40 ml/min as calculated by the Cockcroft-Gault formula In females with childbearing potential, or men with partners of child bearing potential, willingness to use adequate contraception for a minimum duration of 155 days in females and 215 days in males, after last dose of nivolumab Maximal tumor resection has been performed as feasible

Who cannot join

  • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) for urothelial cancer within 4 weeks, or intravesical Bacillus Calmette-Guerin (BCG) within 6 weeks of the first dose of study treatment Prior treatment with any PD-1 or PDL-1 inhibitor
  • The subject has received therapeutic radiation:
  • To the bladder/prostate/rectum pelvis
  • To any other site(s) within 28 days of the first dose of study treatment Obstructive renal failure that is not relieved with stents or nephrostomy tube/s The subject has received any other type of investigational agent within 28 days before the first dose of study treatment Steroid doses greater than an equivalent of prednisone 10 mg daily The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test results at screening >= 2 x the laboratory ULN Uncontrolled hematuria
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders such as uncontrolled arrhythmias or uncontrolled congestive heart failure
Show all 13Show fewer
  • Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Any of the following at the time of screening
  • Active peptic ulcer disease,
  • Active inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
  • Any of the following within 6 months before the first dose of study treatment:
  • History of abdominal fistula
  • Bowel perforation The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee Presence of another invasive malignancy, which required systemic therapy within 12 months of protocol enrollment, except for resected skin cancers or prostate cancer that is in remission Pregnant or nursing women Patient is a candidate for radical cystectomy as a potentially curative option. The patient may not be a candidate for radical cystectomy due to any of the following reasons: comorbidities, patient preference, or physician discretion. Patients with inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., ataxia-telangiectasia, Nijmegen breakage syndrome)

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

Other trials in United States

About this study

Official title: Phase II Trial of Concurrent Nivolumab in Urothelial Bladder Cancer With Radiation Therapy in Localized/Locally Advanced Disease for Chemotherapy Ineligible Patients [NUTRA]

This phase II trial studies how well nivolumab works with radiation therapy in treating patients with urothelial bladder cancer that has spread from its original site of growth to nearby tissues or lymph nodes and are ineligible for chemotherapy. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab and radiation therapy may work better in treating patients with urothelial bladder cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the 12-month rate of progression-free survival (PFS) achieved with the combination of nivolumab, a programmed death (PD-1) inhibitor, and radiation therapy in localized/locally advanced urothelial cancer patients, who are chemotherapy ineligible, to a historical control reference 12-month PFS rate.

SECONDARY OBJECTIVES:

  1. To assess the toxicity of concurrent nivolumab and radiation therapy in urothelial cancer.

II. To determine overall response rate (ORR). III. To determine metastasis-free survival (MFS). IV. To determine overall survival (OS). V. To evaluate the quality of life and bladder functioning during and after the therapy.

VI. To explore the relationships of PD-1 expression, PDL-1 expression, and the Th1/Th2 cytokine ratio to clinical outcomes (response, PFS, MFS, and OS).

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days (2 weeks) for up to 14 courses (6 months) in the absence of disease progression or unacceptable toxicity. Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.

After completion of study treatment, patients are followed up every 3 months for 12 months.

Being tested
Nivolumab, Radiation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called 946414-94-4, BMS-936558, MDX-1106, NIVO

    Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days (2 weeks) for up to 14 courses (6 months) in the absence of disease progression or unacceptable toxicity. Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.

  • RadiationRadiation

    Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.

Study groups in NCT03421652
Study groupRoleWhat they receive
Treatment (nivolumab, radiation therapy)ExperimentalGiven IV
Receives: Drug: Nivolumab; Radiation: Radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    PFS distribution will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve for PFS will be generated along with the Hall-Wellner 90% confidence band, and a display of the number of patients at risk at several time points, below the X-axis. Summary statistics (12-month PFS rate, median PFS, etc.) will be calculated from the K-M life table, each one with its respective 90% confidence interval (CI).

    Measured: From date of registration to date of first documented disease relapse/progression, or death from urothelial cancer whichever occurs first, assessed up to 12 months

Secondary outcomes (6)
  1. Overall Response Rate (ORR)

    ORR will be estimated among all patients. Frequency distributions of best response will be generated. The point estimate of the ORR will be computed, along with its 95% (Wilson type) CI.

    Measured: Up to 12 months

  2. Metastasis-free Survival (MFS)

    MFS will be calculated as a rate at 1 year with a 90% confidence interval from the K-M life tables.

    Measured: From registration to the appearance of metastases or cancer related death, assessed up to 12 months

  3. Overall Survival (OS)

    Summary statistics of OS will be calculated from the K-M life tables. K-M graphs of the censored OS distributions will also be generated.

    Measured: From date of registration to death or last follow up, assessed up to 36 months

  4. Quality of Life (QOL) and Bladder Functioning Questionnaires Assessment

    The QOL score will be measured pre therapy, during therapy and after therapy to compare the changes.

    Measured: Up to 12 months

  5. PD-1 and PDL-1 Expression Analysis Using Immunohistochemistry (IHC)

    PD-1 status will be checked on pre-therapy tumor tissue and will be correlated with the primary endpoint. Also, the PDL-1 status will be checked on pre-therapy tumor tissue and will be correlated with the primary endpoint.

    Measured: Up to 12 months

  6. Th1/Th2 Cytokine Ratio Analysis

    The continuous markers (e.g., tumor infiltrating lymphocyte [TIL]s, Th1/Th2 cytokine ratio, etc.) will be summarized with standard descriptive statistics. These descriptive analyses of the serum markers will be performed for each time point at which the each marker is determined. Response (CR/PR vs not) will be modeled as a function of a dichotomized version of pre-study the continuous (ungrouped) markers (e.g., TILs from tissue, and the Th1/Th2 cytokine ratio from serum). The statistical goal of these exploratory analyses is to obtain the point and 95% CI estimates of the OR, and to simply determine the direction and approximate magnitude of these associations for use in planning a subsequent study. Censored PFS will be modeled as a function of a dichotomized version of the continuous (ungrouped) markers (e.g., TILs from tissue, and the Th1/Th2 cytokine ratio using Cox modelling strategy.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2018
  2. Study start24 Apr 2018
  3. Primary completion23 Mar 2023
  4. Study completion23 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03421652
Sponsor's protocol ID
2016-195
Status last verified
Aug 2023
First submitted
10 Jan 2018
Last updated
4 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Radiation in people with Stage II Bladder Urothelial Carcinoma AJCC v6 and v7 and Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, run by Barbara Ann Karmanos Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: From date of registration to date of first documented disease relapse/progression, or death from urothelial cancer whichever occurs first, assessed up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.

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