A Single-Blind, Multicenter, Placebo-Controlled, Sequential Design Study Evaluating the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram - n/a

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2008-004967-21-FR
• Date of registration: 10/12/2008
• Prospective Registration: Yes
• Primary sponsor: Pharma Mar, S.A.
• Public title: A Single-Blind, Multicenter, Placebo-Controlled, Sequential Design Study Evaluating the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram - n/a
• Scientific title: A Single-Blind, Multicenter, Placebo-Controlled, Sequential Design Study Evaluating the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram - n/a
• Date of first enrolment: 22/12/2008
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004967-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: no; Single blind: yes; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: sequential design; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men or women between 18 and 65 years of age, inclusive
2. Subjects with locally advanced or metastatic solid tumors who have received three or less prior lines of systemic chemotherapy will be included.
3. Subjects must have relapsed or had progressive disease following standard of care treatment with chemotherapy prior to enrollment, or intolerant to prior standard of care treatment with chemotherapy
4. Subjects who have had total prior anthracycline over 260 mg/m2 should have LVEF within normal limits, according to the institutional guidelines. A MUGA (multigated acquisition) scan or 2-d echocardiogram must be performed within 6 weeks before enrollment.
5. Blood pressure (after the subject is supine for 10 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
6. A 12-lead ECG consistent with normal cardiac conduction and function, showing:
· Sinus rhythm
· Pulse rate between 45 and 90 bpm
· QTc interval < or = 500 ms (based on the mean of 3 tracings (Fridericia corrected values))
· QRS interval of <110 ms
· PR interval <200 ms
· Morphology consistent with healthy cardiac conduction and function
7. Non-smoker (has not used any tobacco products for at least 6 months before study drug administration)
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
9. Adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values within 7 days before Day 1:
– hemoglobin = 9 g/dL
– absolute neutrophil count (ANC) = 1,500/µL
– platelet count =100,000/µL
– serum creatinine < or = 1.5 mg/dL (< or = 132.6 µmol/L), if not then 24 hour urine creatinine clearance must be = 50 mL/min
– creatine phosphokinase (CPK) < or = upper limit of normal (ULN)
10. Hepatic function variables
– total bilirubin < or = 1.5 ULN
– total alkaline phosphatase (ALP) < or =1.5 ULN, or if >1.5 ULN, ALP liver fraction or 5’ nucleotidase must be < or = ULN
– AST and ALT must be < or = 2.5 x ULN
11. Adequate recovery from surgery, at least 2 weeks from last dose of hormonal therapy, at least 3 weeks from prior chemo- or biological therapy, at least 3 weeks from receiving radiotherapy, at least 4 weeks after or a period 10 times the drug’s half life (approximately 75 days), whichever is longer, before the first dose of the study drug is scheduled from the last experimental anticancer therapy, and 6 weeks in the case of receipt of nitrosoureas or mitomycin C, provided all side effects from these therapies have resolved to grade 1 or less according to the National Cancer Institute – Common Terminology Criteria of Adverse Events (NCI_CTCAE, Version 3)
12. Must be able to receive dexamethasone or its equivalent
13. If female, must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study
14. If female of child bearing potential, must have a negative serum ß-human chorionic gonadotropin (ß-hCG)] pregnancy test at screening; and a negative urine pregnancy test on Day –1 of the treatment phase
15. If male, must agree to use an adequate contraception method as deemed appropriate by the investigator (e.g., vasectomy, double-barrier, partner using effective contraception) and to not don
Exclusion criteria:
1. Subjects treated with more than three prior chemotherapy regimens (including adjuvant therapy)
2. Previous exposure to trabectedin
3. Subjects with CNS metastasis
4. Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone
5. Have heart rhythm disturbances, unusual T wave and U wave (if present) morphology, blood pressure outside of normal range, a history of cardiac failure, myocardial infarction, or cardiomyopathy, or a history of additional risk factors for torsade de pointes (e.g. heart failure, electrolyte abnormalities, family history of Long QT Syndrome)
6. Have any skin condition likely to interfere with ECG electrode placement, a history of breast implant or thoracic surgery likely to cause abnormality in electrical conduction
7. Subjects who at screening are on medication (refer to Attachment 7) that is known to prolong the QT interval or who are on CYP3A4 inhibitors or inducers. Subjects must have been off these medications for a mimimum of 5 half-lives.
8. History of or current clinically significant medical illness including (but not limited to), congestive heart failure, angina pectoris, or other cardiac disease, documented myocardial infarction within one year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmia, symptomatic brain metastases or leptomeningeal disease, significant pulmonary disease, including bronchospastic respiratory disease, uncontrolled diabetes, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, positive serology results for hepatitis B surface antigen (HBsAg), or hepatitis C antibodies, or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the study results
9. Subjects unwilling or unable to have a central catheter
10. History of illegal drug use or alcohol abuse within 6 months before study drug administration
11. If a woman, breast-feeding or planning to become pregnant during the study
12. Preplanned surgery or procedures that would interfere with the conduct of the study
13. Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.



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

Health Condition(s) or Problem(s) studied

- to assess the potential effects of trabectedin on the QT/QTc interval duration measured by electrocardiograms (ECGs) in subjects with advanced solid tumor malignancies when administered at a therapeutic dose.
MedDRA version: 9.1 Level: LLT Classification code 10007050 Term: Cancer

Intervention(s)

Trade Name: Yondelis 0,25 mg powder for concentrate for solution for infusion
Product Name: YONDELIS (Trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trabectedin
CAS Number: 114899-77-3
Current Sponsor code: R279741, JNJ-17027907-AAA, ET-743
Other descriptive name: ecteinascidin 743
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 1.3-1.5
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Yondelis 1 mg powder for concentrate for solution for infusion
Product Name: YONDELIS (Trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trabectedin
CAS Number: 114899-77-3
Current Sponsor code: R279741, JNJ-17027907-AAA, ET-743
Other descriptive name: ecteinascidin 743
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 1.3-1.5
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are to assess the survival, the safety and pharmacokinetics of trabectedin.

Main Objective: The objective of this study is to assess the potential effects of trabectedin on the QT/QTc interval duration measured by electrocardiograms (ECGs) in subjects with advanced solid tumor malignancies when administered at a therapeutic dose.

Primary end point(s): The primary pharmacodynamic endpoint will be the difference in delta-QTc at each scheduled time point.

Secondary ID(s)

ET743-OVC-1001

2008-004967-21-BE

Ethics review

Status: Approved
Approval date: 11/12/2008
Contact:

Results

• Results available: Yes
• Date Posted: 05/08/2016
• Date Completed: 12/12/2009
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-004967-21/results