AzTrials
AzTrials

Muscle Invasive Bladder CancerPhase 2NCT03294304

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

A Phase 2 study testing Nivolumab, Cisplatin and Gemcitabine in people with Muscle Invasive Bladder Cancer, run by Masonic Cancer Center, University of Minnesota at 3 sites in United States.

Completed

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

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Muscle Invasive Bladder Cancer
What is being tested?
Nivolumab, Cisplatin and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
3 sitesUnited States
Study dates
29 Jan 2018to 1 Jul 2021
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

  • 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
Show all 16Show fewer
  • 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.
  • Ability to provide written consent prior to the initiation of any research related procedures.

Who cannot join

  • 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
  • Hearing loss of 25 dB at two contiguous frequencies with testing required if a patient has hearing loss - At the investigator's discretion, and after discussion with the patient, this exclusion may be waived if the potential benefit of cisplatin therapy is felt to outweigh the risk of further hearing loss.
  • CTCAE v4 Grade 2 or higher peripheral neuropathy,
  • New York Heart Association Class III or IV heart failure
Show all 33Show fewer
  • 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.
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C antibody. Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Active tuberculosis or BCG infection
  • Active infection requiring systemic antibiotics for more than 7 days within 3 days prior to Cycle 1, Day 1. Prophylactic short-term antibiotics will be allowed.
  • Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
  • Persisting toxicity from prior therapy (NCI CTCAE v4.03 Grade >1); however alopecia or other Grade <2 AEs not constituting a safety risk, based on Investigator's judgement, are acceptable.
  • History of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma).
  • Prior allogeneic stem cell or solid organ transplant.
  • Known primary central nervous system (CNS) malignancy.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted but patients with psoriasis require a baseline ophthalmologic exam to rule out ocular manifestations. Rash must cover less than 10% of body surface area (BSA) and must be well controlled at baseline and only requiring topical steroids.
  • Any other chronic medical condition or psychiatric condition, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy. Patients on androgen deprivation therapy as part of adjuvant therapy after radiation for prostate cancer or patients on adjuvant hormonal therapies for breast cancer will be allowed if they are being considered for curative intent for bladder cancer.
  • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
  • Concomitant use of systemic corticosteroids at physiologic doses or <10 mg/day of prednisone or equivalent.
  • Concomitant use of another investigational agent and/or treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five halflives of the investigational product, whichever is longer).
  • Use of bisphosphonate therapy for osteoporosis will be allowed if started prior to study enrollment.

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Masonic Cancer Center - University of Minnesota

    Minneapolis, Minnesota, 55455

  • Huntsman Cancer Institute - University of Utah Health

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: BLASST-1 (Bladder Cancer Signal Seeking Trial): Phase II Trial of Neoadjuvant Nivolumab With Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Radical Cystectomy

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.

Keywords
MIBC, UC, Immunotherapy, Bladder Cancer, Neoadjuvant, Nivolumab, Cisplatin, Gemcitabine
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

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

  • NivolumabDrug

    Also called Opdivo

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

  • CisplatinDrug

    Also called Platinol

    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.

  • GemcitabineDrug

    Also called Gemzar

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

Study groups in NCT03294304
Study groupRoleWhat they receive
Nivolumab, Cisplatin, & GemcitabineExperimentalNot described
Receives: Drug: Nivolumab; Drug: Cisplatin; Drug: Gemcitabine

What is being measured

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

  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.

    Measured: Surgery Day 1

Secondary outcomes (11)
  1. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 1)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment Day 1 of cycle 1

  2. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 1)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment Day 8 of cycle 1

  3. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 2)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment Day 1 of cycle 2

  4. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 2)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treament day 8 of cycle 2

  5. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 3)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment day 1 of cycle 3

  6. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 3)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment day 8 of cycle 3

  7. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 4)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment day 1 of cycle 4

  8. Safety of Nivolumab With Gemcitabine/Cisplatin (Cycle 4)

    Count of participants with Adverse Events related to Nivolumab with Gemcitabine/Cisplatin

    Measured: Treatment day 8 of cycle 4

  9. Safety of Nivolumab With Gemcitabine/Cisplatin

    Incidence of Adverse Events

    Measured: 30 Days +/- 7 Days after last chemotherapy

  10. Safety of Nivolumab With Gemcitabine/Cisplatin

    Incidence of Adverse Events

    Measured: 4 weeks post radical cystectomy

  11. Count of Participants Experiencing Progression Free Survival (PFS)

    Count of participants experiencing Progression Free Survival (PFS)

    Measured: Every 3 Months for 2 Years

Timeline

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

  1. First posted27 Sep 2017
  2. Study start29 Jan 2018
  3. Primary completion5 Jun 2020
  4. Study completion1 Jul 2021

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
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03294304
Sponsor's protocol ID
2017LS039
Status last verified
Nov 2021
First submitted
22 Sep 2017
Last updated
16 Dec 2021
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Cisplatin and Gemcitabine in people with Muscle Invasive Bladder Cancer, run by Masonic Cancer Center, University of Minnesota at 3 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 16 inclusion and 33 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 16 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 16 Dec 2021). 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?

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) (time frame: Surgery Day 1). 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 16 Dec 2021.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in