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)

NCT04876313 | Unknown Phase 2

• 2 other identifiers: NURE-Combo2020-005050-20
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Muscle-Invasive Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  To assess whether nab-paclitaxel plus nivolumab results in pathological complete response (herein referred to as either "ypT0N0M0" or "pCR") in patients with clinical T2-4aN0M0 MIBC who cannot receive or refuse to receive cisplatin-based chemotherapy. Absence of any residual viable tumor in the radical cystectomy specimen. Two independent pathologists, blinded to the study findings, with \>10 years of experience in genitourinary tumors will independently evaluate the response.

  Change from Screening after radical cystectomy

Secondary Outcomes (5)

• pathological downstaging

  screening, 14 days after final combined treatment, 3 weeks until 12 months post-radical cystectomy, 3 months until 12 months post-adjuvant nivolumab

• radiological response

  screening, 14 days after final combined treatment, 3 weeks until 12 months post-radical cystectomy, 3 months until 12 months post-adjuvant nivolumab

• Number of participants with treatment related adverse events as assessed by CTCAE v5.0 and EAU recommendations

  From date of Screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months

• event-free survival

  From date of Screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months

• overall survival

  From date of Screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months

Study Arms (1)

Combined Drugs

EXPERIMENTAL

Participants received 4x3 weekly cycles of 360 mg Nivolumab + 125 mg/m\^2 Nab-paclitaxel IV on days 1 and 8, then they had cystectomy after that partecipants received adjuvant nivolumab 360 mg IV Q3W X13 cycles

Drug: Nivolumab + Nab-paclitaxel; Drug: Nivolumab

Interventions

Nivolumab + Nab-paclitaxel DRUG

4x3 weekly cycles of 360 mg nivolumab + 125 mg/m\^2 nab-paclitaxel IV on days 1 and 8

Also known as: Nivolumab + Abraxane

Combined Drugs

Nivolumab DRUG

360 mg IV Q3W x 13 cycles

Also known as: Adjuvant Nivolumab

Combined Drugs

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Genitourinary Medical Oncology - IRCCS San Raffaele Hospital and Scientific Institute

Milan, MI, 20132, Italy

RECRUITING

Related Publications (1)

• Mercinelli C, Moschini M, Cigliola A, Mattorre B, Tateo V, Basile G, Cogrossi LL, Maiorano BA, Patane DA, Raggi D, Pastorino GL, Re C, Colecchia M, Luciano R, Colombo R, Brembilla G, De Cobelli F, Briganti A, Pavlick DC, Ross JS, Montorsi F, Bellone M, Necchi A. First Results of NURE-Combo: A Phase II Study of Neoadjuvant Nivolumab and Nab-Paclitaxel, Followed by Postsurgical Adjuvant Nivolumab, for Muscle-Invasive Bladder Cancer. J Clin Oncol. 2024 Dec 10;42(35):4196-4205. doi: 10.1200/JCO.24.00576. Epub 2024 Sep 6.

  PMID: 39241203 DERIVED

MeSH Terms

Interventions

Nivolumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins

Central Study Contacts

Andrea Necchi

CONTACT

+39 0226435789; necchi.andrea@hsr.it

Rossella Miotti

CONTACT

+39 0226435789; Miotti.rossella@hsr.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor - Head of Genitourinary Medical Oncology

Model Details: Patients with muscle-invasive urothelial bladder carcinoma, not eligible or denying standard neoadjuvant therapy

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 6, 2021
• Study Start: January 27, 2022
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: April 6, 2022

Record last verified: 2022-03

Locations

IT (1)