Clofarabine treatment for advanced or metastatic urothelial carcinoma

Clofarabine Therapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma: a Phase 1/2 Dose-Escalation Study

This study will test whether clofarabine is safe and can shrink tumors in adults with locally advanced or metastatic urothelial carcinoma who have already received or declined standard treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical University of Vienna (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Vienna)
• Trial ID: NCT07034053 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, dose-escalation study seeks to define the maximum tolerated dose of clofarabine in adults with metastatic or unresectable locally advanced urothelial carcinoma. The trial will characterize clofarabine pharmacokinetics and monitor patients for safety, tolerability, and preliminary anti-tumor activity. Eligible participants have histologically confirmed disease and have previously received or refused standard-of-care therapy, and must meet specified laboratory and performance-status criteria. The study is conducted at the Department of Urology, Medical University of Vienna, using escalating dose cohorts to identify recommended dosing for further testing.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed metastatic or unresectable locally advanced urothelial carcinoma, ECOG 0–2, adequate blood counts and liver/renal function, and prior standard therapy failure or refusal are the intended candidates.

Not a fit: Patients with significant renal or hepatic impairment, low blood counts, ECOG performance status >2, or those who remain eligible for effective approved therapies are unlikely to benefit from this early-phase trial.

Why it matters

Potential benefit: If successful, clofarabine could offer a new systemic treatment option to control disease in patients with advanced urothelial carcinoma who have exhausted standard therapies.

How similar studies have performed: Clofarabine is approved for certain pediatric leukemias and showed promising preclinical activity in urothelial cancer, but clinical use in urothelial carcinoma is largely novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

* Patients with histologically or cytologically confirmed urothelial carcinoma, radiologically documented metastatic or unresectable locally advanced disease
* Patients who have already received standard treatment and did not benefit from it, or patients who have refused standard therapy
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Absolute neutrophil count (ANC) greater than or equal to 1500.
* White blood cell (WBC) count greater than 3.0.
* Platelets greater than or equal to 100.
* Hemoglobin greater than 9.0 g/dL.
* Adequate hepatobiliary function as indicated by the following laboratory values: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
* Adequate renal function as indicated by the following laboratory values: Serum creatinine ≤ 1.0 mg/dL; if serum creatinine \> 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \> 60 mL/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation
* Adequate cardiac function (NYHA cardiac III-IV excluded)
* Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
* Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
* Willing and able to provide informed consent

Exclusion Criteria:

* Received previous treatment with clofarabine
* Current concomitant chemotherapy, radiation therapy, or immunotherapy
* Prior radiation therapy to the pelvis
* Currently participation in other investigational drug studies or having received other investigational drugs within the previous 30 days
* Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. In particular: a) New York Heart Association classification stage II, III, or IV congestive heart failure; b) Coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infraction) within 3 months of first dose of study drug; c) Any other primary cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
* Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
* Any medical condition that requires chronic use of oral high-dose corticosteroids (in excess of 1 mg/kg/day) (low-dose corticosteroid for pre-medication purposes are allowed).
* Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
* Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in-situ carcinoma or cervical intraepithelial neoplasia regardless of disease-free duration are eligible for this study if definitive treatment for the condition has been completed; Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on PSA value are eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed
* Had currently active gastrointestinal disease, or prior surgery that might affect the ability of the participants to absorb oral Clofarabine.
* Had prior treatment with a known nephrotoxic drug within 2 weeks of the first dose of study drug, unless the participants had a calculated GFR \>30 at 2 time points no \<7 days apart during the 2- week period prior to the first dose of study drug.
* Positive human immunodeficiency virus (HIV) test.
* Female patients who are pregnant/breastfeeding.

Where this trial is running

Vienna

• Department of Urology, Medical University of Vienna — Vienna, Austria (Recruiting)

Study contacts

• Principal investigator: Shahrokh F. Shariat Prof. Dr., Professor — Department of Urology, Medical University of Viernna
• Study coordinator: Ekaterina Laukhtina Dr., Medical Doctor

Conditions Advanced Urothelial Carcinoma; Metastatic Urothelial Cancer