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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Oct 2023 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516586-37-00

EudraCT number

2022-003592-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety

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

Secondary objectives 3

1. To characterize the pharmacokinetics of Clofarabine in patients with metastatic or locally advanced urothelial carcinoma.
2. To assess treatment efficacy of Clofarabine in patients with metastatic or locally advanced urothelial carcinoma.
3. To assess safety and tolerability of Clofarabine in patients with metastatic or locally advanced urothelial carcinoma.

Conditions and MedDRA coding

Urothelial carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patients with histologically or cytologically confirmed urothelial carcinoma, radiologically documented metastatic or unresectable locally advanced disease
2. Patients who have already received standard treatment and did not benefit from it, or patients who have refused standard therapy
3. Age ≥ 18 years
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
5. Absolute neutrophil count (ANC) greater than or equal to 1500
6. White blood cell (WBC) count greater than 3.0
7. Platelets greater than or equal to 100
8. Hemoglobin greater than 9.0 g/dL
9. 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
10. 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
11. Adequate cardiac function (NYHA cardiac III-IV excluded)
12. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
13. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
14. Willing and able to provide informed consent

Exclusion criteria 12

1. Received previous treatment with clofarabine
2. Current concomitant chemotherapy, radiation therapy, or immunotherapy
3. Currently participation in other investigational drug studies or having received other investigational drugs within the previous 30 days
4. 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
5. 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)
6. 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)
7. 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
8. 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
9. Had currently active gastrointestinal disease, or prior surgery that might affect the ability of the participants to absorb oral Clofarabine
10. 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
11. Positive human immunodeficiency virus (HIV) test
12. Female patients who are pregnant/breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Maximum tolerated dose (MTD)

Secondary endpoints 7

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Urology

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Urology

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications