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

Phase 1/2

Recruiting

• Conditions: Urothelial carcinoma

• Registration Number: 2024-516586-37-00
• Lead Sponsor: Medical University Of Vienna

Brief Summary

To define maximum tolerated dose of Clofarabine in patients with metastatic or locally advanced urothelial carcinoma

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-14
• Last Update Posted: 2024-10-14

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

Patients with histologically or cytologically confirmed urothelial carcinoma, radiologically documented metastatic or unresectable locally advanced disease

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

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

Exclusion Criteria

Received previous treatment with 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

Current concomitant chemotherapy, radiation therapy, or immunotherapy

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD)		Maximum tolerated dose (MTD)

Secondary Outcome Measures

Name	Time	Method
Objective response (OR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1		Objective response (OR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Duration of response (DOR) (radiographic)		Duration of response (DOR) (radiographic)
Time to progression (radiographic)		Time to progression (radiographic)
Progression-free survival (PFS)		Progression-free survival (PFS)
Overall survival (OS)		Overall survival (OS)
Treatment-related adverse events evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 5.0)		Treatment-related adverse events evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 5.0)
Pharmacokinetics parameters of Clofarabine including maximum serum concentration (Cmax) and area under the concentration-time curve (AUC)		Pharmacokinetics parameters of Clofarabine including maximum serum concentration (Cmax) and area under the concentration-time curve (AUC)

Trial Locations

Locations (1)

Medical University Of Vienna; 🇦🇹 Vienna, Austria

Medical University Of Vienna

🇦🇹Vienna, Austria

Shahrokh Shariat

Site contact

+4314040026150

shahrokh.shariat@meduniwien.ac.at