Clofarabine Therapy in Locally Advanced or Metastatic Urothelial Carcinoma

NCT07034053 | Recruiting Phase 1 DMC

• 1 other identifier: CLOFARABINE_UC
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1/2 study will evaluate the maximum tolerated dose, efficacy, and safety of clofarabine in patients with advanced or metastatic urothelial cancer.

Conditions

Advanced Urothelial Carcinoma; Metastatic Urothelial Cancer

Outcome Measures

Primary Outcomes (1)

• Determining the maximum tolerated dose (MTD)

  The objective of the dose selection phase is to determine the maximum tolerated dose (MTD) or confirm that the start dose level of clofarabine is safe. The MTD is defined as the highest dose at which the probability of toxicity remains below the target toxicity threshold. MTD estimation will be based on the observed dose-dependent incidence rate of dose-limiting toxicity (DLT) within the first 28 days of dosing (Cycle 1). Patients eligible for MTD evaluation include: * Those who completed Cycle 1 and took at least 80% of the required total dose of the study drug (protocol-defined dose reductions will not be considered noncompliance). * Those who discontinued during Cycle 1 due to a DLT.

  From the start of study drug administration through the first 28 days of dosing (Cycle 1), based on the observed incidence of dose-limiting toxicity (DLT) and evaluation of maximum tolerated dose (MTD)

Secondary Outcomes (7)

• Objective response rate (ORR)

  From the date of study treatment start until the date of the best documented objective response (for a maximum duration of 36 months).

• Duration of response (DOR)

  From the date of the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (for a maximum duration of 36 months).

• Progression-free survival (PFS)

  From the date of study treatment start until the date of the first observed progression or date of death due to any cause, if death occurs before progression is documented (for a maximum duration of 36 months).

• Overall survival (OS)

  From the date of study treatment start until the date of death due to any cause (for a maximum duration of 36 months).

• Safety and tolerability endpoints

  Day 1 up to 90 days after last dose of study drug.

Study Arms (1)

Patients with urothelial carcinoma treated with clofarabine

EXPERIMENTAL

Drug: Clofarabine

Interventions

Clofarabine DRUG

Patients receive i.v. clofarabine in a dose-escalation regimen

Patients with urothelial carcinoma treated with clofarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ekaterina Laukhtina: lead

Study Sites (1)

Department of Urology, Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Related Publications (6)

• Foss FM, Parker T. A Phase I Dose-Escalation Study of Clofarabine in Patients with Relapsed or Refractory Low-Grade or Intermediate-Grade B-Cell or T-Cell Lymphoma. Oncologist. 2018 Apr;23(4):397-e30. doi: 10.1634/theoncologist.2017-0658. Epub 2018 Feb 7.

  PMID: 29438091 BACKGROUND

• Kantarjian HM, Erba HP, Claxton D, Arellano M, Lyons RM, Kovascovics T, Gabrilove J, Craig M, Douer D, Maris M, Petersdorf S, Shami PJ, Yeager AM, Eckert S, Abichandani R, Faderl S. Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol. 2010 Feb 1;28(4):549-55. doi: 10.1200/JCO.2009.23.3130. Epub 2009 Dec 21.

  PMID: 20026805 BACKGROUND

• Kantarjian HM, Gandhi V, Kozuch P, Faderl S, Giles F, Cortes J, O'Brien S, Ibrahim N, Khuri F, Du M, Rios MB, Jeha S, McLaughlin P, Plunkett W, Keating M. Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol. 2003 Mar 15;21(6):1167-73. doi: 10.1200/JCO.2003.04.031.

  PMID: 12637486 BACKGROUND

• Zhenchuk A, Lotfi K, Juliusson G, Albertioni F. Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1.

  PMID: 19576186 BACKGROUND

• Gutmann M, Ertl IE, Herek P, Vician P, Pirker C, Nossing C, Brettner R, Lemberger U, Grausenburger R, Batlogg K, Baumfried O, Prantl I, Singh N, Laukhtina E, Oszwald A, Wasinger G, Comperat E, Berger W, Shariat SF, Englinger B. Clofarabine Has a Superior Therapeutic Window as compared to Gemcitabine in Preclinical Bladder Cancer Models. Eur Urol Oncol. 2024 Dec;7(6):1166-1170. doi: 10.1016/j.euo.2024.05.001. Epub 2024 May 16.

  PMID: 38755094 BACKGROUND

• Ertl IE, Lemberger U, Ilijazi D, Hassler MR, Bruchbacher A, Brettner R, Kronabitter H, Gutmann M, Vician P, Zeitler G, Koren A, Lardeau CH, Mohr T, Haitel A, Comperat E, Oszwald A, Wasinger G, Clozel T, Elemento O, Kubicek S, Berger W, Shariat SF. Molecular and Pharmacological Bladder Cancer Therapy Screening: Discovery of Clofarabine as a Highly Active Compound. Eur Urol. 2022 Sep;82(3):261-270. doi: 10.1016/j.eururo.2022.03.009. Epub 2022 Apr 4.

  PMID: 35393162 BACKGROUND

MeSH Terms

Interventions

Clofarabine

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Shahrokh F. Shariat Prof. Dr., Professor

  Department of Urology, Medical University of Viernna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ekaterina Laukhtina Dr., Medical Doctor

CONTACT

+43 (0)1 40400-26315; ekaterina.laukhtina@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Sponsor-Investigator

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: June 24, 2025
• Study Start: October 24, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

AU (1)