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Advanced Urothelial CarcinomaPhase 1/2NCT07034053

Clofarabine Therapy in Locally Advanced or Metastatic Urothelial Carcinoma

A Phase 1/2 study testing Clofarabine in people with Advanced Urothelial Carcinoma and Metastatic Urothelial Cancer, run by Ekaterina Laukhtina at 1 site in Austria.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Clofarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteAustria
Study dates
24 Oct 2023to Nov 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ekaterina Laukhtina Dr., Medical Doctor contact

+43 (0)1 40400-26315

ekaterina.laukhtina@meduniwien.ac.at

Austria1 site, 1 recruiting

  • Department of Urology, Medical University of Vienna

    Vienna, 1090

    Ekaterina Laukhtina Dr., Medical Doctor, +43 (0)1 40400-26315, ekaterina.laukhtina@meduniwien.ac.at

    Recruiting

Other trials in Austria

About this study

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

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

Read the detailed description

Clofarabine is an antimetabolite chemotherapeutic agent used as a subsequent line of treatment in pediatric patients with leukemia. In preclinical studies, it showed promising results, surpassing the effectiveness of the current standard of care. The study aims to define the maximum tolerated dose of clofarabine in patients with metastatic or locally advanced urothelial carcinoma. It also seeks to characterize the pharmacokinetics of clofarabine and assess the efficacy, safety, and tolerability of the treatment. The study population consists of patients with histologically confirmed urothelial carcinoma and radiologically documented metastatic or unresectable locally advanced disease, who have already received standard-of-care treatment. The study will be performed using a dose-escalation regimen.

Being tested
Clofarabine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ClofarabineDrug

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

Study groups in NCT07034053
Study groupRoleWhat they receive
Patients with urothelial carcinoma treated with clofarabineExperimentalNot described
Receives: Drug: Clofarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Objective response rate (ORR)

    Objective response rate (ORR) is defined as the percentage of patients whose best response is either a complete response (CR) or partial response (PR). Patients for whom best tumor response is not CR or PR, as well as patients without any efficacy assessment will be considered non-responders. According to RECIST v1.1, confirmation of PR and CR is not required considering the nature of the study and the protocol requirements.

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

  2. Duration of response (DOR)

    Duration of response (DOR) (for PR and CR) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR. The actual dates the tumor scans were performed will be used for this calculation. DOR for patients who have not progressed or died at the time of analysis will be censored at the date of their last tumor assessment.

    Measured: 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).

  3. Progression-free survival (PFS)

    Progression-free survival (PFS) is defined as the time (days) from start of study treatment to date of first observed disease progression (investigator's radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented. The actual date that the tumor scan was performed will be used for this calculation. If a tumor assessment is performed over more than one day (e.g. scans for chest and abdomen done on different days for the same evaluation), the earliest date will be used for the calculation of PFS. For patients without documented radiological or clinical progression or death at the time of analysis, PFS will be censored at the last actual visit date of tumor evaluation.

    Measured: 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).

  4. Overall survival (OS)

    Overall survival (OS) is defined as the time from start of study treatment to death due to any cause. Patients alive at the date of data cut-off for analysis will be censored at the last date known to be alive. If a patient is lost to follow-up before any assessment after assignment to treatment, this patient will be censored at 1 day.

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

  5. Safety and tolerability endpoints

    Individual listings of adverse events will be provided. Treatment-related adverse events evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5.0). Adverse events will be reported as absolute numbers (n) and relative frequencies (%). Visualization of the results will be presented with help of tables and diagrams.

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

  6. Area under the concentration-time curve (AUC)

    The concentration-times courses of all analytes will be tabulated by dose level.

    Measured: Day 1 up to the date of the last dose of study drug.

  7. Maximum serum concentration (Cmax) of Clofarabine

    The concentration-times courses of all analytes will be tabulated by dose level.

    Measured: Day 1 up to the date of the last dose of study drug.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2025
  2. Study start24 Oct 2023
  3. Primary completionNov 2028 (estimated)
  4. Study completionNov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07034053
Sponsor's protocol ID
CLOFARABINE_UC
Status last verified
Jun 2025
First submitted
4 Jun 2025
Last updated
26 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 29438091

  • 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.

    PubMed 20026805

  • 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.

    PubMed 12637486

  • 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.

    PubMed 19576186

  • 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.

    PubMed 38755094

  • 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.

    PubMed 35393162

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Clofarabine in people with Advanced Urothelial Carcinoma and Metastatic Urothelial Cancer, run by Ekaterina Laukhtina at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ekaterina Laukhtina Dr., Medical Doctor (+43 (0)1 40400-26315, ekaterina.laukhtina@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determining the maximum tolerated dose (MTD) (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07034053, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.

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