BLASST-1 (Bladder Cancer Signal Seeking Trial): Nivolumab, Gemcitabine, and Cisplatin in Treatment of Muscle Invasive Bladder Cancer (MIBC) Undergoing Cystectomy

NCT03294304 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 2017LS039
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multi-center Phase II study to determine the safety and efficacy of nivolumab when given in combination with cisplatin and gemcitabine as neoadjuvant treatment in patients with muscle-invasive bladder cancer (MIBC) prior to standard of care radical cystectomy. Patients will receive neoadjuvant treatment with nivolumab in combination with gemcitabine-cisplatin (GC) every 3 weeks for 4 treatment cycles over 12 weeks followed by standard of care radical cystectomy.

Conditions

Muscle Invasive Bladder Cancer

Keywords

MIBC; UC; Immunotherapy; Bladder Cancer; Neoadjuvant; Nivolumab; Cisplatin; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• Pathologic Response Rate (PaR) at Time of Radical Cystectomy. PaR is Defined as Absence of Residual MIBC at Cystectomy in the Surgical Specimen (Pathologic Down-staging to ≤pT1pN0 Which Includes pT0, pT1, pTa and pTis)

  Incidence of Measurable Disease "pT" in the TNM staging system refers to the size and extend of the primary tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b. pTa refers to noninvasive papillary carcinoma. pTis refers to carcinoma in situ (CIS) or a "flat tumor" stage. pN refers to lymph nodes. N0 mans cancer has not spread to nearby lymph nodes.

  Surgery Day 1

Secondary Outcomes (11)

• Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 1)

  Treatment Day 1 of cycle 1

• Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 1)

  Treatment Day 8 of cycle 1

• Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 2)

  Treatment Day 1 of cycle 2

• Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 2)

  Treament day 8 of cycle 2

• Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 3)

  Treatment day 1 of cycle 3

Study Arms (1)

Nivolumab, Cisplatin, & Gemcitabine

EXPERIMENTAL

Drug: Nivolumab; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Nivolumab DRUG

Nivolumab will be given at a fixed dose of 360 mg IV over 30 minutes on Day 8 every 21 days for 4 cycles.

Also known as: Opdivo

Nivolumab, Cisplatin, & Gemcitabine

Cisplatin DRUG

Cisplatin will be given at 70 mg/m2 IV over 30 minutes on Day 1 every 21 days, and based on treating physician's discretion, split-dose cisplatin can be given at 35 mg/m2 IV Day 1 and Day 8 every 21 days for 4 cycles.

Also known as: Platinol

Nivolumab, Cisplatin, & Gemcitabine

Gemcitabine DRUG

Gemcitabine will be given at 1000 mg/m2 IV over 30 minutes on days 1, 8, and every 21 days for 4 cycles.

Also known as: Gemzar

Nivolumab, Cisplatin, & Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Diagnosis of MIBC (predominantly urothelial carcinoma) with clinical stage T2-T4a and N\<1 disease (solitary lymph node measuring \< 2 cm) and M0 and deemed eligible for radical cystectomy.
• Age ≥ 18 years
• ECOG Performance Status of 0 or 1.
• Required initial laboratory values within 14 days of study enrollment:
• Absolute Neutrophil Count ≥ 1500 cells/mm\^3
• Platelets ≥ 100,000 cells/mm\^3
• Hemoglobin ≥ 9.0 g/dL
• Bilirubin ≤ 1.5 times the upper limit of normal (ULN) for the institution (For patients with known Gilbert's disease: bilirubin ≤ 3 x ULN)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN for the institution
• Creatinine clearance ≥ 50 ml/min by Cockcroft-Gault formula or 24 hour urinary clearance (CrCl = \[140-age (years)\] x actual weight (kg) / \[72 x serum Cr (mg/dL)\] (if patient is female multiply the above by 0.85) or 24 hour urinary creatinine clearance.
• Alkaline phosphatase ≤ 2.5 x ULN for the institution
• INR and aPTT ≤ 1.5 x ULN if not on therapeutic anticoagulation. Patients receiving therapeutic anticoagulation will be allowed if maintained on a stable dose.
• Females of childbearing potential and males who are not surgically sterile and with partners of childbearing potential must agree to use effective contraception during study treatment for 5 months for females and 7 months for males after the last dose of nivolumab.
• Ability to provide a signed and dated consent or have a legally authorized representative to provide written and signed consent prior to the initiation of any research related procedures.
• Patient must agree to submission of archived tumor (20-25 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness) from TURBT and radical cystectomy tissues. If archived samples are not available fresh tissue will be used.

You may not qualify if:

• Presence of N2-3 or M1 disease.
• Ineligible to receive cisplatin by meeting one or more of the following criteria;
• Creatinine clearance of \< 50 mL/min
• CTCAE v4 Grade 2 or higher peripheral neuropathy,
• New York Heart Association Class III or IV heart failure
• ECOG performance status 2 or higher.
• Prior systemic therapy (intravenous) is not permitted. Prior intravesical therapies including intravesical gemcitabine is permitted for non-muscle invasive disease (i.e. T1 or lower).
• Prior treatment with cisplatin for bladder cancer.
• Prior treatment with anti-PD-1, CTLA-4, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
• Prior therapeutic radiation to the bladder.
• Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (\>New York Heart Association Class 2), stroke, serious cardiac arrhythmia.
• Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
• Pregnancy, lactation, or breast-feeding. Women of childbearing potential must have a negative urine pregnancy test at screening.
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Masonic Cancer Center - University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Huntsman Cancer Institute - University of Utah Health

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Konety Badrinath
• Organization: Masonic Cancer Center, University of Minnesota

brkonety@umn.edu

612-625-1655

Study Officials

• Badrinath Konety, MD, MBA

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

• Shilpa Gupta, MD

  Cleveland Clinic Taussig Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

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: September 22, 2017
• First Posted: September 27, 2017
• Study Start: January 29, 2018
• Primary Completion: June 5, 2020
• Study Completion: July 1, 2021
• Last Updated: December 16, 2021
• Results First Posted: December 16, 2021

Record last verified: 2021-11

Locations

US (3)