Phase II multicenter,open-label, clinical and pharmacokinetic study of Aplidin® as a 3-hour infusion every 2 weeks, in patients with advanced or metastatic transitional cell carcinoma of the urothelium, relapsing or progressing after first line chemotherapy

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2004-001118-15-ES
• Date of registration: 31/03/2005
• Prospective Registration: No
• Primary sponsor: Pharma Mar, S.A
• Public title: Phase II multicenter,open-label, clinical and pharmacokinetic study of Aplidin® as a 3-hour infusion every 2 weeks, in patients with advanced or metastatic transitional cell carcinoma of the urothelium, relapsing or progressing after first line chemotherapy
• Scientific title: Phase II multicenter,open-label, clinical and pharmacokinetic study of Aplidin® as a 3-hour infusion every 2 weeks, in patients with advanced or metastatic transitional cell carcinoma of the urothelium, relapsing or progressing after first line chemotherapy
• Date of first enrolment: 27/10/2004
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001118-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent obtained from the patient before starting any study-specific procedure. If any patient is unable to give consent, it may be obtained from the patient’s legal representative if in accordance with local laws and regulations.
2. Transitional cell carcinoma of the urothelium of the bladder, urether or renal pelvis, with the following characteristics:
· Confirmed pathological diagnosis.
· Advanced (locally advanced or metastatic) and / or non-resectable disease (surgical exeresis does not eradicate all the macroscopic disease).
· With documented objective progression according to the RECIST criteria within 6 months prior to registration.
· Presence of at least one measurable lesion (RECIST). In case of a single measurable lesion, pathological proof of malignancy is mandatory.
3. One previous line of systemic chemotherapy. All prior therapies should have been finished at least 3 weeks before patient registration.
4. Prior radiotherapy: a minimum of 4 weeks (8 weeks in case of extensive prior radiotherapy) must have elapsed between the end of the prior radiotherapy and entry into the protocol. Previously irradiated lesions may not be used as indicator lesions unless a new lesion has occurred in a previously irradiated area.
5. Recovery from any toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.
6. Age > 18 years.
7. Performance status (ECOG) < 2
8. Life expectancy > 3 months.
9. Adequate renal, hepatic, and bone marrow function (assessed < 14 days before inclusion in the study):
· Neutrophil count ³ 1.5 x 109/L
· Platelet count ³ 100 x 109/L
· Haemoglobin ³ 10 g/dL
· Creatinine clearance ³ 40 ml/min (calculated from the Cockcroft and Gault formula, Appendix 3)
· Serum bilirubin * 1.5 mg/dL and alkaline phosphatase * 2.5 x ULN (< 5 x ULN in case of extensive bone metastases)
· AST, ALT < 2.5 x ULN (< 5 x ULN in case of liver metastasis).
· Albumin > 25 g/L
10. Left ventricular ejection fraction within normal limits.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Prior therapy with Aplidin®.
2. More than one line of prior systemic chemotherapy.
3. Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods.
If subject is female, she is eligible to enter and participate in this study if she is of:
a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,
b. child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and agrees to one of the following:
· Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug (a minimum of 5 plasma half-lifes); or,
· Female sterilization; or,
· Sterilization of male partner; or,
· Implants of levonorgestrel; or,
· Injectable progestogen; or,
· Oral contraceptive (combined or progestogen only); or,
· Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or,
· Double barrier method (2 physical barriers or 1 physical barrier plus spermicide); or,
· Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year.
Subject taking oral contraceptives should have been on a stable regimen for at least 2 months prior to screening

4. History of another neoplastic disease. The exceptions are:
· non-melanoma skin cancer
· carcinoma in situ of any site
· any other cancer curatively treated and no evidence of disease for at least 10 years.
5. Known symptomatic cerebral or leptomeningeal involvement.
6. Other relevant diseases or adverse clinical conditions:
· Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study.
· Uncontrolled arterial hypertension (i.e. current arterial diastolic blood pressure over 100 mmHg)
· Uncontrolled cardiac supraventricular arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).
· Cardiac ventricular arrhythmia.
· History of significant neurological or psychiatric disorders
· Active infection.
· Myopathy or any clinical situation that causes significant and persistent elevation of CK (>2.5 ULN in two different determinations performed with one week appart)
· Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)
· Limitation of the patient’s ability to comply with the treatment or follow-up protocol.
· Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months)
7. Treatment with any investigational product in the 30 days period before inclusion in the study.
8. Known hypersensitivity to Aplidin®, mannitol, cremophor EL, or ethanol




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

More than 90% of bladder carcinomas are transitional cell carcinomas (TCC) derived from the uroepithelium. About 6% to 8% are squamous cell carcinomas, and 2% are adenocarcinomas. Adenocarcinomas may be either of urachal origin or of nonurachal origin; the latter type is generally thought to arise from metaplasia of chronically irritated transitional epithelium.

Intervention(s)

Product Name: Aplidin
Product Code: APLD
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Cyoctodepsin
Current Sponsor code: APLD
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-
INN or Proposed INN: Cyoctodepsin
Current Sponsor code: APLD
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Main Objective: To assess the anti-tumor activity of Aplidin® administered as a 3 h iv infusion every 2 weeks, in patients with advanced or metastatic transitional cell carcinoma of the urothelium, relapsing or progressing after first line chemotherapy.

Secondary Objective: Evaluation of Pharmacokinetics of this schedule of Aplidin® in this patient population.
To further investigate the safety profile of Aplidin® given as 3-hour IV infusion every 2 weeks in this patient population.

Primary end point(s): 1. Objective tumor response (CR or PR) according to RECIST

Secondary ID(s)

APL-B-005-02

Ethics review

Status: Approved
Approval date: 20/07/2004
Contact:

Results

• Results available: Yes
• Date Posted: 31/07/2016
• Date Completed: 20/03/2007
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-001118-15/results