E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients who completed standard dose chemotherapy for the treatment of non-Hodgkin lymphoma or the adjuvant treatment of breast cancer or colorectal cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025322 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006200 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009944 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038038 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy: Efficacy of five weeks ranolazine on post-chemotherapy diastolic dysfunction at echocardiography, and/or PDS at SPECT, and/or Nt-proBNP elevation. Safety: Objective and subjective tolerability of five weeks ranolazine in post-chemotherapy cancer patients |
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E.2.2 | Secondary objectives of the trial |
1. Objective and subjective tolerability of six months ranolazine in post-chemotherapy cancer patients 2. Objective and subjective tolerability of five weeks to six months ranolazine in comparison with best standard of therapy. 3. This study is designed to prospectively assess: 3.1 The apparent incidence of cardiotoxicity (symptomatic or at laboratory tests) among patients exposed to standard dose chemotherapy regimens. 3.2 Mechanistic relations of reversible perfusion defects with diastolic dysfunction at echocardiography and/or Nt-proBNP or TnI levels in cancer patients. 3.3 Efficacy of five weeks to six months ranolazine at reducing the incidence of any cardiac event (symptomatic or at laboratory tests) in comparison with patients who remained on standard institutional follow-up. 3.4 To evaluate the incidence of cardiotoxicity in the study s global population (patients on ranolazine, best standard of therapy, standard institutional follow-up). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18-70 years 2. Eastern Cooperative Oncology Group performance status of 0 to 1 3. total serum bilirubin < 2.0 mg/dL 4. serum creatinine level < 2.0 mg/dL 5. normal ECG 6. LVEF ≥ 50% at echocardiography 7. normal E/A and DcT at echocardiography 8. no significant perfusion defect at SPECT 9. able to release written informed consent 10. women of childbearing potential must have a negative serum pregnancy test; they agree on avoiding pregnancy by adequate contraceptive precautions (e.g., double barrier methods), or abstinence, during both chemotherapy and subsequent ranolazine therapy (if applicable) 11. male patients are informed of the mutagenic and embryotoxic effects of chemotherapy; in agreement with their partner, they accept not to concur in a pregnancy by adopting adequate contraceptive precautions, or abstinence, during chemotherapy. |
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E.4 | Principal exclusion criteria |
1. pregnancy or nursing 2. women with HER-2+ breast cancer requiring post-chemotherapy trastuzumab 3. prior chemotherapy or medastinal irradiation 4. patients with mediastinal lymphoma liable to irradiation after completing chemotherapy 5. long QTc, LVEF < 50% or altered E/A, or significant perfusion defects, at screening ECG, echocardiography, and SPECT 6. hypertension 7. any clinically documented heart disease 8. any other medical conditions that required treatment over the past 3 months with ACEI, ABR, Ca2+ antagonists, β blockers, nitrates, diuretics 9. diabetes mellitus 10. dislipidemia 11. BMI > 30 12. prior steroid pulse therapy for unrelated diseases 13. severe renal impairment 14. moderate or severe hepatic impairment 15. cerebral vascular accidents within the past 3 months 16. severe psychopathy 17. chronic obstructive lung disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Efficacy will be evaluated as improvement or disappearance of abnormalities detected at the post-chemotherapy assessment. To evaluate the efficacy of 5 weeks ranolazine, the abnormalities detected in a given patient at the post-chemotherapy assessment will be compared to the same abnormalities detected in that patient at the 5 weeks early reassessment. Safety: The tolerability of 5 weeks ranolazine will be evaluated by describing all drug-related adverse events such as constipation, nausea, dizziness or any abnormality at laboratory tests. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |