Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma

Running, not enrolling · Phase 1

Conditions studied: Infiltrating Urothelial Carcinoma, Sarcomatoid Variant, Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Unresectable Urothelial Carcinoma

In brief

This phase I trial studies the side effects and best dose of belinostat when given together with durvalumab in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Belinostat is a potential anti-cancer drug, known as a histone deacetylase (HDAC) inhibitor, which means that belinostat stops the activity of HDAC enzymes (an enzyme is a protein that in small amounts can speed up a biological reaction). HDAC enzymes play an important role in cell growth and cell death. Giving durvalumab and belinostat may improve the body's ability to fight cancer.

Key facts

Study ID

NCT05154994

Run by

University of Utah

People needed

9

Starts

2022-01-14

Expected to finish

2028-02-01

Last updated by the study team

2026-05-07

Who can join

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

You may qualify if…

• Male or female subject aged >= 18 years
• Histologically confirmed urothelial carcinoma with metastatic disease or with unresectable, locally advanced disease. Variant histology, including, but not limited to, neuroendocrine, sarcomatoid, and squamous differentiation are permitted to enroll
• Patients must meet one or more of the following criteria:
• Has progressed on at least one prior therapy; or
• Has declined standard therapy; or
• Is not a suitable candidate for standard therapy
• The discussion regarding the choice of standard therapy offered, if available, and patient's choice and reason(s) to decline standard therapy should be documented clearly in the research chart.
• Patients may have progressed on immune checkpoint inhibitor therapy
• Body weight > 30 kg
• Subject must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by computed tomography (CT) or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Absolute neutrophil count (ANC) >= 1500/mm\^3
• Platelet count >= 100,000/mm\^3
• Hemoglobin >= 10 g/dL Hemoglobin < 10 g/dL due to hematuria at the time of treatment is acceptable as long as there is evidence of adequate bone marrow function in the opinion of the investigator.
• Total 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]) =< 3 x institutional ULN
• Patients with liver metastases will be allowed to enroll with AST and ALT levels =< 5 x ULN
• Estimated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
• Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
• Highly effective contraception for both male and female subjects throughout the study and at least 4 months after last study treatment administration
• Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically non-significant and/or stable on supportive therapy
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
• Estimated life expectancy of at least 12 weeks

You may not qualify if…

• Homozygous for UGT1A1*28 allele or heterozygous or homozygous for UGT1A1*60 orGilbert syndrome
• Subject has received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy =< 14 days or within 5 half-lives before starting study treatment, whichever is shorter
• Prior treatment with durvalumab
• Subject has received radiotherapy =< 14 days before the first dose of study treatment. Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe
• Subjects who have undergone major surgery =< 3 weeks before starting study drug or who have not fully recovered from major surgery
• Known additional malignancy that is active and/or progressive and requiring treatment.
• Known brain metastases or cranial epidural disease
• Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment
• Current evidence of uncontrolled, clinically significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before the first dose
• Uncontrolled hypertension defined as a sustained systolic blood pressure >= 160 mmHg or a diastolic blood pressure >= 100 mmHg despite optimal management
• Note: Patients with uncontrolled hypertension who are not optimally managed may be rescreened once controlled hypertension is achieved
• Note: Patients with uncorrectable prolonged corrected QT (QTc) (Bezet formula) > 480 msec or concomitant use of medications(s) with a known risk of inducing Torsade de Pointes if such treatment cannot be discontinued or switched to a different medication before starting the study drug
• Note: If a single electrocardiogram (ECG) shows a QTc with an absolute value > 480 msec, two additional ECGs approximately 2 minutes apart must be performed within 30 minutes of the initial ECG, and the average of these three consecutive results for QTc will be used
• Adrenal insufficiency
• Interstitial lung disease (ILD)
• Subjects with congenital long QT syndrome
• Patients currently on or who will require valproic acid for any medical condition during the study
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [except for diverticulosis], 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 principal investigator

Where it is running

• Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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