Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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.
Full description
PRIMARY OBJECTIVE:
I. Determine the pathologic complete response(pCR) 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.
Enrollment
Sex
Ages
Volunteers
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
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:
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:
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
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:
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:
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
History of allogenic organ transplantation
Primary purpose
Allocation
Interventional model
Masking
24 participants in 1 patient group
Loading...
Central trial contact
The Ohio State Comprehensive Cancer Center; Rebecca Williams
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal