Effect of Lurbinectedin (PM01183) on Cardiac Repolarization (QTc Duration) in Patients with Solid Tumors

Phase 1

• Conditions: - small cell lung cancer (SCLC)- head and neck carcinoma (H&N)- neuroendocrine tumors (NETs)- biliary tract carcinoma- endometrial carcinoma- BRCA 1/2-associated metastatic breast carcinoma- carcinoma of unknown primary site- germ cell tumors (GCTs)- Ewing?s family of tumors (EFTs); MedDRA version: 18.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-000206-18-ES
• Lead Sponsor: PharmaMar S.A., Sociedad Unipersonal

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07-10
• Last Update Posted: 3 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1) To be enrolled in clinical trial PM1183-B-005-14
2) Voluntarily signed and dated informed consent to participate in this QT evaluation study
3) Qualifying 12-lead ECG (between Day -10 and Day -2 before first IMP administration) consistent with normal cardiac conduction and function, that will be read by the central laboratory, showing:
a) Sinus rhythm.
b) Heart rate between 45 and 100 beats per min (bpm).
c) QTcF ? 500 ms.
d) QRS interval <110 ms.
e) PR interval <220 ms.
4) Blood pressure between 90 and 150 mmHg systolic, inclusive, and not higher than 90 mmHg diastolic
5) Serum electrolyte levels within ten days prior to the first infusion ? grade 1 [National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0]:
a) Corrected serum Ca: 2.0 ? 2.9 mmol/l.*
b) K: 3 ? 5.5 mmol/l. **
c) Mg: 0.5 ? 1.23 mmol/l.
* Corrected serum Ca for albumin = Measured serum Ca (mmol/l) + 0.2 * [4.0
? Measured albumin (g/dl)].
** Patients with K < 4 mmol/l could have their potassium repleted to allow
them to participate. If so, K should be re-tested to confirm that new levels of
serum K are within the specified range.
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 25
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Age > 65 years
2) Eastern Cooperative Oncology Group performance status (ECOG PS) = 2 *
3) Heart rhythm disturbances (e.g., atrial fibrillation), unusual T wave and U wave (if present) morphology, personal or family history of Long QT Syndrome, complete left bundle branch block, permanent ventricular pacemaker, or Brugada Syndrome
4) Significant ischemic coronary disease, New York Heart Association (NYHA) class III or IV congestive heart failure, myocardial infarction, or unstable angina within the last six months
5) Any skin condition likely to interfere with ECG electrode placement, or history of breast implant or thoracic surgery likely to cause abnormality in electrical conduction
6) Prior exposure to anthracyclines at a cumulative dose of doxorubicin (or equivalent) > 450 mg/m²
7) Patients who are at screening on QT-prolonging medication (rated as 1 at APPENDIX 1: Lists of drugs that prolong the QT interval and/or induce torsades de pointes ventricular arrhythmia), if it cannot be interrupted at least 48 hours before each ECG assessment
* Note that PM1183-B-005-14 eligibility criteria permit ECOG PS ? 2.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified