Study of CAbozantinib in Combination with AtezolizumaB for Muscle-Invasive BladdEr Cancer

Running, not enrolling · Phase 2

Conditions studied: Bladder Cancer

In brief

This is an open-label phase II study assessing the activity of cabozantinib combined with atezolizumab in patients with resectable muscle-invasive urothelial carcinoma who are ineligible for cisplatin-based therapy or decline cisplatin-based therapy. Each cycle equals 21 days. The dose of atezolizumab is 1200 mg IV flat dose every 3 weeks (Day 1) plus cabozantinib 40 mg orally daily (Day 1 through Day 21). Patients will receive three cycles of treatment prior to cystectomy unless they discontinue treatment for unacceptable toxicity or progressive disease by RECIST v1.1 or withdraw consent.

Key facts

Study ID

NCT04289779

Run by

Deepak Kilari

People needed

46

Starts

2020-05-21

Expected to finish

2025-12-01

Last updated by the study team

2024-12-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥18 years at the time of consent.
• ECOG Performance Status of ≤ 2 within 28 days prior to registration.
• Histological or cytologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle-invasion is allowed.
• Archival tissue is required, if available. The tissue should be identified at screening and shipped after registration, prior to Cycle 3 Day 1. If archival tissue is not available a repeat biopsy is not required, and the subject may still be eligible. Archival tissue should have been obtained within 60 days prior to registration.
• Urothelial carcinoma should be the predominant component (≥ 50%). NOTE: Any neuroendocrine differentiation is not permitted.
• Clinical stage T2-T4aN0/xM0 disease.
• No clinical or radiographic evidence for locally advanced or metastatic disease.
• Medically appropriate candidate for radical cystectomy as assessed by surgeon.
• Patients must have a contraindication to cisplatin or decline cisplatin based neoadjuvant chemotherapy. Absolute or relative contraindication to cisplatin, defined as one or more of the following within 28 days prior to registration (Grading per CTCAE v5):
• Creatinine clearance < 60 mL/min (Cockcroft-Gault formula will be used to calculate creatinine clearance)
• Grade ≥ 2 hearing loss
• Grade ≥ 2 neuropathy
• No radiation therapy < 4 weeks of registration. NOTE: prior radiation therapy to the bladder is not allowed.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatment.
• Must have a life expectancy of at least 12 weeks at registration.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration. See protocol for more details.
• White blood cell count ≥ 2500/mm3 (≥2.5 GI/L)
• Absolute Neutrophil Count (ANC) ≥ 1500/mm3 (≥1.5 GI/L) without G-CSF
• Platelet Count (Plt) ≥ 100,000/mm3 (≥100 GI/L) without transfusion
• Hemoglobin (Hgb) ≥ 9 g/dL (may be transfused)
• Calculated creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula
• Urine protein/creatinine ratio (UPCR) ≤ 2 mg/mg if no hematuria and ≤ 3.5 mg/mg if hematuria noted
• Calcium or ionized calcium; Calcium <12 mg/dL or corrected serum calcium < ULN or ionized calcium <1.5 mmol/L
• Bilirubin ≤ 1.5 × upper limit of normal (ULN); if documented Gilbert's syndrome bilirubin must be ≤ 3 x ULN

You may not qualify if…

• Prior treatment with cabozantinib.
• Severe infection within 4 weeks prior to initiation of study treatment per investigator assessment. Examples include hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Active infection requiring systemic therapy.
• Active tuberculosis.
• Prior history of stem cell or solid organ transplantation.
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the study or within 5 months after the last dose of study drug.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Treatment with any investigational drug within 30 days prior to registration.
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or other cancer for which the subject has been disease-free for at least five years. Patients with localized prostate cancer who are either being followed by an active surveillance program OR planning to undergo definitive treatment are also eligible.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. NOTE: Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies are excluded. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded.
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab or cabozantinib formulation.
• Prior treatment with the following is prohibited unless otherwise specified:
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed).
• Any type of small molecule kinase inhibitor within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy within 4 weeks before first dose of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest imaging.
• Significant cardiovascular disease, such as:
• New York Heart Association Congestive Heart Failure Class II or greater.
• Myocardial infarction, unstable angina or unstable arrhythmias within 3 months of enrollment.
• History of stroke or TIA within 3 months of enrollment.
• Other clinically significant arterial vascular disease within 6 months of enrollment (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis). Prior history of adequately treated venous thromboembolism > 7 days prior to C1D1 on stable dose of therapeutic anticoagulation is permitted.
• Subjects with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed.
• History of leptomeningeal disease.

Where it is running

• Washington University School of Medicine — St Louis, Missouri, United States
• John Theurer Cancer Center — Hackensack, New Jersey, United States
• University of Rochester Medical Center — Rochester, New York, United States
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States
• Virginia Commonwealth University — Richmond, Virginia, United States
• Froedtert and The Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.