Trial Title:
Gemcitabine/Cisplatin Plus Cemiplimab With or Without Fianlimab in Localized Muscle-invasive Bladder Cancer (NeoSTOP-IT)
NCT ID:
NCT06571708
Condition:
Bladder Cancer
Muscle-Invasive Bladder Carcinoma
Conditions: Official terms:
Urinary Bladder Neoplasms
Gemcitabine
Cemiplimab
Conditions: Keywords:
Urothelial Predominant Histology
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Gemcitabine 1000 mg/m^2 IV
Arm group label:
Group 1: Gemcitabine/Cisplatin/Cemiplimab
Arm group label:
Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin 70 mg/m^2 IV or renally-dosed split-dose cisplatin 35 m/m^2 IV
Arm group label:
Group 1: Gemcitabine/Cisplatin/Cemiplimab
Arm group label:
Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab
Intervention type:
Drug
Intervention name:
Cemiplimab
Description:
Cemiplimab 350mg IV
Arm group label:
Group 1: Gemcitabine/Cisplatin/Cemiplimab
Arm group label:
Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab
Other name:
REGN 2810
Intervention type:
Drug
Intervention name:
Fianlimab
Description:
Fianlimab 1600mg IV
Arm group label:
Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab
Other name:
REGN3767
Summary:
The goal of this clinical trial is to learn if gemcitabine/cisplatin plus cemiplimab with
or without fianlimab works to treat bladder cancer in adults. The main question it aims
to answer is: Can gemcitabine, cisplatin, and cemiplimab with or without fianlimab treat
bladder cancer?
Participants will be randomly selected (like the loss of a coin) to treatment with
gemcitabine, cisplatin, cemiplimab, and fianlimab or gemcitabine, cisplatin, and
cemiplimab.
Participants will:
- Undergo transurethral resection of bladder tumor (TURBT) followed by the start of
treatment, receive 4 cycles of treatment (21 day cycles)
- After 4 cycles of treatment, patients will undergo repeat maximal TURBT with imaging
- Participants with a complete response will continue maintenance cemiplimab or
cemiplimab/fianlimab for 13 more cycles with imaging every 3 months
- Participants without a complete clinical response will undergo cystectomy (bladder
surgery).
Detailed description:
This is a phase 2, open-label, randomized trial with continuous toxicity monitoring to
ensure safety using Bayesian toxicity monitoring, which will evaluate treatment with
doublet platinum-based chemotherapy (gemcitabine and cisplatin) plus cemiplimab
(REGN2810) with or without fianlimab (REGN3767) for localized muscle-invasive bladder
cancer (MIBC). Participants will be randomized to 4 cycles of 3 weeks each (12 weeks
total) with gemcitabine, cisplatin, and cemiplimab with or without fianlimab.
Participants achieving a clinical complete response will continue 13 more cycles of
immunotherapy (39 weeks total). The total duration of systemic treatment, including
neoadjuvant therapy, will be 52 weeks.
In addition to the actual time on treatment, there will be time off treatment for
recovery after neoadjuvant treatment and before adjuvant treatment. First, between the
neoadjuvant phase and cystoscopy (with TURBT for residual disease), there will be up to 4
weeks off treatment. In between the cystoscopy/TURBT and start of adjuvant immunotherapy,
there will be an additional up to 4 week interval for recovery. Participants will have
regularly scheduled study visits at the clinical site on Day 1 and Day 8 of every
three-week cycle in the neoadjuvant setting, where continuous assessment, including
treatment response and safety assessments, will be performed. These will include
laboratory tests, taking of vital signs, and physical examinations. In the adjuvant
setting for participants who continue to maintenance immunotherapy, participants will
have regularly scheduled study visits at the clinical site on Day 1 of every three-week
cycle.
Response to treatment will be determined by three modalities. First, CT scans (chest,
abdomen, and pelvis with and without contrast) to ensure no metastatic disease. For
participants who are unable to get a CT scan w/ contrast due to renal function (or any
other reason), an MRI with and without contrast may be used instead. Scans are required
at baseline and every 3 months in the adjuvant setting for participants who continue on
with maintenance immunotherapy. Second, all participants will undergo post-treatment
cystoscopy every 3 months while on treatment. Third, all participants will undergo
post-treatment urine cytology every 3 months while on treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Willing and able to provide written informed consent for the trial.
- Age ≥18 years of age on day of signing informed consent.
- Life expectancy > 12 months.
- Performance status of 0-1 using the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.
- Histologically confirmed muscle-invasive urothelial carcinoma of the bladder defined
as T2-T3, N0, M0 stage. Mixed histology is permitted if there is a urothelial
component. Upper tract disease in not permitted.
- Prior Bacillus Calmette-Guerin (BCG) or other intravesical treatment of non-muscle
invasive bladder cancer is permitted if completed at least 6 weeks prior to
initiating study treatment. Only one course (includes induction + maintenance) of
BCG or intravesical therapy is permitted.
- No metastatic disease based on cross-sectional imaging.
- Considered cisplatin eligible based on protocol specified criteria.
- Not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.
- Agree to pre- and post-treatment TURBT as well as surveillance with cystoscopies,
cross-sectional imaging, and urine cytology unless medically contraindicated in the
opinion of the treating physician, and discussed with the principal investigator
Exclusion Criteria:
- Concurrent upper urinary tract (i.e., ureter, renal pelvis) invasive urothelial
carcinoma. (NOTE: Patients with history of non-invasive (Ta, Tis) upper tract
urothelial carcinoma that has been definitively treated with at least one post-
treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no
evidence of residual disease are eligible).
- Received prior immune checkpoint inhibitors (including anti-PD-1, anti-PD-L1,
anti-CTLA4, anti-LAG-3 or any other antibody or drug specifically targeting T-cell
co-stimulation or checkpoint pathways ), as well as cellular vaccines, cellular
therapies, or systemic oncolytic virus therapy.
- Received bladder-directed radiation therapy previously for bladder cancer.
- Received prior systemic chemotherapy for muscle-invasive bladder cancer.
- Receiving any other investigational agents concurrently or within 4 weeks of start
of treatment.
- Had a solid organ or hematologic transplant.
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that required
systemic treatment with immunosuppressive agents. The following are
non-exclusionary: vitiligo, childhood asthma that has resolved, residual
hypothyroidism that requires only hormone replacement, psoriasis not requiring
systemic treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a
dose greater than 10mg/day of prednisone equivalent) or any other form of
immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily
prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Has a history of myocarditis.
- Patients with another active second malignancy other than non-melanoma skin cancers.
- Has a known history of, or any evidence of, interstitial lung disease or active
noninfectious pneumonitis.
- Has an active infection requiring systemic therapy.
- History or current evidence of significant (Common Terminology Criteria for Adverse
Events (CTCAE) grade ≥2) local or systemic infection (eg, cellulitis, pneumonia,
septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the
first dose of trial medication.
- Has a history of current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator,
including dialysis.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus
(HBV), or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that
is related to, or results in chronic infection.
- Is pregnant or is a breastfeeding woman.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Columbia University Irving Medical Center
Address:
City:
New York
Zip:
10032
Country:
United States
Contact:
Last name:
Alexander Z Wei, MD
Phone:
212-305-5874
Email:
aw3056@cumc.columbia.edu
Contact backup:
Last name:
Nurse Navigator
Phone:
212-305-5098
Email:
cancerclinicaltrials@cumc.columbia.edu
Start date:
November 2024
Completion date:
December 2028
Lead sponsor:
Agency:
Columbia University
Agency class:
Other
Collaborator:
Agency:
Regeneron Pharmaceuticals
Agency class:
Industry
Source:
Columbia University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06571708
