Trial Title:
Futibatinib in Combination With Durvalumab Prior to Cystectomy for the Treatment of Muscle-Invasive Bladder Cancer Patients Who Are Ineligible for Cisplatin-based Therapy
NCT ID:
NCT06263153
Condition:
Bladder Urothelial Carcinoma
Muscle Invasive Bladder Carcinoma
Stage II Bladder Cancer AJCC v8
Stage IIIA Bladder Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Urinary Bladder Neoplasms
Durvalumab
Futibatinib
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (futibatinib, durvalumab, radical cystectomy)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (futibatinib, durvalumab, radical cystectomy)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Durvalumab
Description:
Given IV
Arm group label:
Treatment (futibatinib, durvalumab, radical cystectomy)
Other name:
Imfinzi
Other name:
Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
Other name:
MEDI-4736
Other name:
MEDI4736
Intervention type:
Drug
Intervention name:
Futibatinib
Description:
Given PO
Arm group label:
Treatment (futibatinib, durvalumab, radical cystectomy)
Other name:
Lytgobi
Other name:
TAS-120
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (futibatinib, durvalumab, radical cystectomy)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Radical Cystectomy
Description:
Undergo radical cystectomy
Arm group label:
Treatment (futibatinib, durvalumab, radical cystectomy)
Other name:
Complete Cystectomy
Summary:
This phase II trial tests how well the combination of futibatinib and durvalumab given
before cystectomy works in treating patients with muscle-invasive bladder cancer (MIBC)
who are ineligible for cisplatin-based therapy. Cisplatin-based therapy is the standard
of care for patients with MIBC. However, many patients cannot receive standard therapy
due to poor renal function, peripheral neuropathy, poor functional status, or clinically
significant heart failure. Futibatinib may stop the growth of tumor cells by blocking
some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that may
interfere with the ability of tumor cells to grow and spread. Radical cystectomy is a
surgery to remove all of the bladder as well as nearby tissues and organs. Giving
futibatinib in combination with durvalumab before surgery may be an effective treatment
option for patients with MIBC who are ineligible for cisplatin-based therapy.
Detailed description:
PRIMARY OBJECTIVE:
I. Determine the pathologic complete response rate of neoadjuvant combination futibatinib
and durvalumab in patients with MIBC and fibroblast growth factor receptor (FGFR)
overexpression.
SECONDARY OBJECTIVES:
I. Determine the safety of this neoadjuvant regimen. II. Assess the pathologic
downstaging rate. III. Evaluate overall survival (OS) and progression free survival
(PFS). IV. Evaluate delay in cystectomy.
EXPLORATORY OBJECTIVES:
I. Evaluate potential predictive biomarkers. II. Assess changes in the tumor
microenvironment in pre- and post-treatment tumor samples in participants.
OUTLINE:
Patients receive futibatinib orally (PO) once daily (QD) on days 1-28 and durvalumab
intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 28
days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Patients then undergo radical cystectomy within 4-12 weeks. Patients also undergo
computed tomography (CT) and magnetic resonance imaging (MRI) during screening and on the
trial and also undergo blood sample collection on the trial.
After completion of study treatment, patients are followed up at 30 days, and then every
3 months for 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Able to provide signed informed consent
- Female or male subjects >= 18 years old
- Bodyweight >30kg
- FGFR1, 2, or 3 overexpression as defined by a score of 3+ or 4+ on ribonucleic acid
(RNA) in-situ hybridization (RNAScope assay)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Histologically confirmed urothelial carcinoma of the bladder
- Mixed histologies are permitted if urothelial carcinoma is the predominant
histology ( >= 50%)
- Clinical stage T2-T4a, N0, M0 disease by trans urethral removal of bladder tumour
(TURBT) and imaging studies (stage II-IIIA per American Joint Committee on Cancer
[AJCC] 2018)
- Refuse or ineligible for cisplatin-based neoadjuvant chemotherapy as defined by any
of the following:
- ECOG performance status (PS) > 1
- Creatinine clearance (calculated or measured) < 60 mL/min as measured by the
Cockcroft-Gault formula
- Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0) grade
>= 2 hearing loss
- CTCAE v 5.0 grade >= 2 neuropathy
- New York Heart Association (NYHA) class > II cardiac dysfunction
- Treatment with anti-PD-1/PD-L1 therapy for non-muscle invasive bladder cancer
(NMIBC) is permitted if it is completed > 3 months before registration
- Eligible for radical cystectomy by the following:
- Fit and planned for radical cystectomy according to local guidelines
- Archival transurethral resection of bladder tumor (TURBT) tissue submission must be
30 unstained slides. If archival tissue is unavailable, the patient must undergo
cystoscopy and biopsy. The tumor sample must contain at least 20% viable tumor
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female premenopausal patients.
- Female subjects of childbearing potential and male subjects must be willing to
completely abstain or agree to use a highly effective method of contraception (i.e.,
less than 1% failure rate), from the time of signing informed consent and for the
duration of study participation through 90 days following the last dose of study
drug.
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) > 1500 per mm^3
- Platelet count >= 100 x 10^9/L
- International normalized ratio (INR) or activated partial thromboplastin time (aPTT)
< 1.5 × upper limit of normal (ULN), unless the patient is receiving anticoagulation
therapy provided INR or PTT is within the therapeutic range of the intended
anticoagulant therapy
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 2.5 x institutional upper limit of normal
- Phosphorus ≤ institutional upper limit of normal (ULN)
- Measured creatinine clearance (CL) > 30 mL/min or calculated creatinine CL > 30
mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for
determination of creatinine clearance
- Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
- Must have a life expectancy of at least 12 weeks
Exclusion Criteria:
- Women who are pregnant or breastfeeding
- Male or female patients of reproductive potential who are not willing to employ
effective birth control from screening to 90 days after the last dose of durvalumab
monotherapy
- Is currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks before the first dose of
trial treatment
- Has upper tract urothelial carcinoma
- Has small-cell carcinoma component on histology
- Evidence of measurable nodal or metastatic disease
- Concurrent anticancer therapy (e.g., chemotherapy, radiation therapy, surgery,
immunotherapy, biologic therapy, hormonal therapy, investigational therapy,
intravesical therapy, or tumor embolization)
- Received prior systemic chemotherapy for muscle-invasive bladder cancer at any time
in the patient's medical history
- Has received anti-PD-1/PD-L1 therapy or FGFR inhibitor previously for MIBC, except
if used in earlier stage urothelial carcinoma such as non-muscle invasive bladder
cancer (NMIBC) and completed > 3 months prior to registration
- Must not have experienced a toxicity that led to permanent discontinuation of
prior immunotherapy.
- All AEs while receiving prior immunotherapy must have completely resolved or
resolved to baseline prior to screening for this study.
- Must not have experienced a ≥Grade 3 immune related AE or an immune related
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE:
Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are
stably maintained on appropriate replacement therapy and are asymptomatic.
- Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE, not have experienced recurrence of
an AE if re-challenged, and not currently require maintenance doses of > 10 mg
prednisone or equivalent per day.
- Underwent major surgery and has not recovered adequately from the intervention's
toxicity and/or complications before starting therapy
- Has an active second malignancy except for low-risk localized prostate cancer on
"watch and wait"
- Subjects with a history of malignancy that has been completely treated, with no
evidence of active cancer for 2 years before enrollment, or subjects with surgically
cured tumors with a low risk of recurrence are allowed to enroll at PI's discretion
(e.g. adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease and effectively treated carcinoma in situ without evidence of
disease).
- Has active cardiac disease, defined as:
- Myocardial infarction or unstable angina pectoris within 3 months of the first
date of study therapy
- Unstable arrhythmias
- Decompensated heart failure
- Uncontrolled hypertension and unstable angina pectoris
- Average QT corrected by the Fridericia formula (QTcF) > 470 msec (males and
females) (Note: If the QTcF is > 470 msec in the first electrocardiography
[ECG], a total of 3 ECGs separated by >= 5 minutes should be performed. If the
average of these 3 consecutive results for QTcF is =< 470 msec, the subject
meets eligibility in this regard.)
- Has any medical condition that may prevent the patient from undergoing radical
cystectomy
- Must be at least 2 weeks beyond high-dose systemic corticosteroids; chronic steroid
use up to 10 mg daily prednisone (or equivalent), intranasal, inhaled, topical
steroids, local steroid injections (e.g., intra articular injection), steroids as
premedication for hypersensitivity reactions (e.g., CT scan premedication) are
permitted
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus
erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with
polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Has a known history of HIV-1/2 with detectable viral load and/or CD4 count < 300/mL
within the previous 3 months or active tuberculosis infection (clinical evaluation
that may include clinical history, physical examination and radiographic findings,
or tuberculosis testing in line with local practice).
- Has detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load
polymerase chain reaction (PCR) if there is a known history of active hepatitis B or
hepatitis C
- History and/or current evidence of significant ectopic mineralization/calcification
including but not limited to the soft tissues, kidneys, intestines, myocardium, and
lungs, except calcified lymph nodes and asymptomatic coronary calcification
- Current evidence of corneal or retinal disorder/ keratopathy including but not
limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration,
keratoconjunctivitis etc., confirmed by ophthalmologic examination
- Have current evidence of endocrine alterations of calcium/phosphate homeostasis
(e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral
calcinosis) unless well controlled
- Have used drugs that are dual p-glycoprotein and strong CYP3A inducers or inhibitors
within 7 days prior to the first dose of the study drug
- Has other concurrent medical or psychiatric conditions that, in the investigator's
opinion, may be likely to confound study interpretation or prevent completion of the
study procedure and follow-up examinations
- Known allergy or hypersensitivity to study drugs or any excipient.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of
investigational product (IP). Note: Patients, if enrolled, should not receive live
vaccine whilst receiving IP and up to 90days after the last dose of IP.
- Has other uncontrolled illnesses, ongoing or active infection, or serious chronic
gastrointestinal conditions associated with diarrhea
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab may be included only after consultation with the
Study Physician
- History of allogenic organ transplantation
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Yuanquan Yang, MD, PhD
Phone:
614-366-2485
Email:
Yuanquan.Yang@osumc.edu
Investigator:
Last name:
Yuanquan Yang, MD, PhD
Email:
Principal Investigator
Start date:
November 1, 2024
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Yuanquan Yang
Agency class:
Other
Collaborator:
Agency:
Gateway for Cancer Research
Agency class:
Other
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06263153
http://cancer.osu.edu
