An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Nivolumab and Nab-paclitaxel Before Radical Cystectomy for Patients With Muscle-invasive Bladder Cancer (NURE-Combo) (NURE-Combo)

  • STATUS
    Recruiting
  • End date
    Jun 26, 2025
  • participants needed
    29
  • sponsor
    IRCCS San Raffaele
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Updated on 26 April 2022
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Summary

To assess whether nivolumab+nab-paclitaxel combination results in patients with muscle-invasive bladder cancer

Description

This is a Phase 2, single-center, open-label, non-randomized study in patients with muscle-invasive urothelial carcinoma of the bladder.

The general framework of the study will be as follows:

A transurethral resection of the bladder for biopsy, histological characterization, and local staging will be executed first. With the aim to improve the sensitivity of CT scan in assessing pelvic lymph-nodes and better assess the local extent of bladder tumor, computed tomography (CT) scan, 18FDG-PET/CT scan, and multiparametric bladder MRI (mpMRI) will be done during screening and before cystectomy to stage and evaluate response.

Eligible patients will receive neoadjuvant treatment: 360 mg nivolumab IV on Day 1 plus 125 mg/m2 nab-paclitaxel on Day 1 and 8, in a 21-day cycle.

A total of 4 cycles are planned before surgery. Surgery will be planned at the time of study inclusion to be done within 3 weeks of the last dose of study drug.

Dose reductions will be applied depending on the severity of AEs, and treatment interruption or discontinuation criteria will be fully described in the protocol.

After surgery, patients will receive 12-month adjuvant therapy with nivolumab 360 mg IV, every 3 weeks.

RECIST v1.1 criteria will be used to assess patient response to treatment by determining tumor size and PFS. Screening assessments should be performed no more than 21 days prior to the start of study treatment. Following the screening assessment, subsequent assessments will be carried out after the administration of the study drugs prior to cystectomy. If an unscheduled assessment is performed and the patient has not progressed, the results should be reported at the next scheduled visit. The method of tumor assessment used at baseline e.g. CT or MRI scans chest, abdomen, pelvis, must be used at each sub-sequent follow-up assessment.

Patients will be monitored carefully for the development of adverse events and will be monitored for clinical and/or radiographic evidence of disease progression according to usual standards of clinical practice. Adverse experiences will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Details
Condition Muscle-Invasive Bladder Carcinoma
Treatment Nivolumab, Nivolumab + Nab-paclitaxel
Clinical Study IdentifierNCT04876313
SponsorIRCCS San Raffaele
Last Modified on26 April 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Female or male subjects, >18 years of age, able to understand and give written informed consent
Histopathologically confirmed urothelial carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern
Fit and planned for RC (according to local guidelines)
ECOG performance status score of 0 or 1
Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (Hemoglobin ≥ 9 g/dL, ANC ≥ 1,500/ mm3, and Platelets ≥ 100,000/ μL)
Adequate hepatic function (Bilirubin ≤ 1.5 IULN, AST and ALT ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin >3 g/dl)
Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation
Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication, and must not be lactating. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 4 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years
Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy
Clinical stage T2-T4aN0M0 MIBC, assessed by CT + PET/CT + mpMRI
The patient accepts to undergo RC
Ineligibility to receive cisplatin-based neoadjuvant chemotherapy based on Galsky's criteria (Galsky MD, et al. J Clin Oncol. 2011 Jun 10;29(17):2432-8) OR refusal to receive neoadjuvant cisplatin-based chemotherapy

Exclusion Criteria

Has received prior systemic anti-cancer therapy including investigational agents and immunotherapy
Prior immunotherapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137
Has received prior radiotherapy on the bladder tumor
Have received a partial cystectomy
Refusal to undergo RC
Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
Has received any antibiotics within 30 days prior to the first dose of study drug
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Note: Participants who have entered the follow-up phase of an investigational study may
participate as long as it has been 4 weeks after the last dose of the previous
investigational agent
Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that
have undergone potentially curative therapy are not excluded. Participants with
low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or
T2a with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) < 10 ng/mL either
treated with definitive intent or untreated in active surveillance that has been
stable for the past year prior to study allocation
Has severe hypersensitivity (≥Grade 3) to nivolumab or nab-paclitaxel and/or any of
its excipients
Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment
Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
or GI perforation within 6 months of enrollment
Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
Have active cardiac disease, defined as
Myocardial infarction or unstable angina pectoris within 6 months of C1D1
History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation), high-grade atrioventricular block, or other cardiac
arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation
that is well controlled with antiarrhythmic medication); history of QT interval
prolongation
NYHA Class III or greater congestive heart failure or left ventricular ejection
fraction of < 40%
Have known history of HIV-1/2 infection
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection
Have other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation or prevent completion of study
procedures and follow-up examinations
High dose systemic corticosteroids (≥20 mg of prednisolone or its equivalent) are not
allowed within 2 weeks of C1D1
Have received or are currently receiving (within the previous 2 weeks) antibiotics
Have a pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI-CTC
criteria due to the potential for neuropathy of nab-paclitaxel
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