E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To establish whether Aspirin can reduce hearing loss/ototoxicity for patients receiving Cisplatin based chemotherapy.
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033109 |
E.1.2 | Term | Ototoxicity |
E.1.2 | System Organ Class | 10013993 - Ear and labyrinth disorders |
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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 |
A trial to identify if Aspirin can reduce hearing loss for patients receiving Cisplatin chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
1. To identify if it is feasible to conduct a Phase III randomised control trial of Aspirin for the same patient population. 2. To measure the degree of hearing loss in patients receiving Cisplatin using a hearing test called the Otoacoustic emissions (OAE) test. 3. To find out if patients can tolerate short-term, large doses of Aspirin taken with Omeprazole without unpleasant side-effects and without having to reduce the dosage of their Cisplatin chemotherapy. 4. Additional consent will be asked to collect blood and urine samples for future ethically approved trials. These samples will be stored at the Cancer Sciences Tissue Bank, Southampton General Hospital. Patients do not have to agree to give these samples if they do not wish to. They will still be able to take part in the main trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Written Informed Consent 2.Any patient deemed fit for chemotherapy with acceptable laboratory values and offered a cumulative dose equal to or more than 200mg/m2 Cisplatin as a single agent or as a combination chemotherapy for malignancy with planned treatment of a maximum of two consecutive days Cisplatin per cycle. 3.Over 18 years old.
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E.4 | Principal exclusion criteria |
1.Previous Cisplatin treatment. 2.Patients with a diagnosis of Nasopharyngeal (or skull base) Carcinoma.Patients with other head and neck tumours being treated with radiotherapy are eligible. 3.Patients where planned Cisplatin is to be given as a split dose regimen on Days 1 to 5 or on Days 1 and 8. 4.Patients receiving therapeutic Aspirin defined as >75mg per day. 5.Previous Haemorrhagic stroke. 6.Inflammatory bowel disease. 7.Patients with absolute contraindications to Aspirin, PPIs or their excipients i.e. allergies, ulcers, renal impairment or use of oral anticoagulants. 8.Haematological or clotting disorders. 9.Patients with symptomatically overt hearing loss which the principal investigator considers should exclude the use of cisplatin. 10.Pregnant or breast-feeding patients. Women of childbearing potential must have a standard negative pregnancy test performed within 7days prior to the start of Trial drug. Both men and women enrolled in this Trial must use adequate birth control. 11.Patients enrolled or who plan to enrol in any other IMP or Surgical Interventional Clinical Trial during the Trial period.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the total difference in hearing before and within 4 to 7 days after finishing treatment, using the pure tone audiogram (PTA) test at frequencies of 6 and 8 kHz in both ears. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All patients will receive a pre-treatment hearing test which will be used as a baseline measurement. Patients will have a second hearing test 4 to 7 days post treatment. They will then have a final hearing test three months after completion of their Cisplatin chemotherapy. |
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E.5.2 | Secondary end point(s) |
1.Total difference in hearing before and 3 months after treatment using the PTA test at frequencies of 6 and 8 kHz in both ears. 2.Common Toxicity Criteria (CTC) – a clinician assessed level of hearing loss. 3.OAE profile, before and 4 to 7 days after treatment, and a further 3 months after finishing treatment). 4.Safety profile assessment (including gastro-intestinal and renal toxicity). 5.Assessment of compliance and concomitant medications as well as total dose of Cisplatin received. 6.Assessment of other PTA test-frequencies including 0.25, 0.5, 1, 2, 3, 4 kHz at baseline and 4 to 7 days after finishing treatment. The final test to be done a further 3 months after treatment. 7.Cisplatin dose-intensity.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• All hearing assessments (PTA and OAE) will be at baseline, 4 to 7 days after finishing Cisplatin treatment and 3 months after finishing Cisplatin treatment. • Common Toxicity Criteria (CTC) – a clinician assessed level of hearing loss at each patient visit. • Safety profile assessment (including gastro-intestinal and renal toxicity) at each patient visit. • Assessment of compliance and concomitant medications as well as total dose of Cisplatin received at each patient visit. • Cisplatin dose-intensity assessed at each patient visit.
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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 | Yes |
E.6.3 | Therapy | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 13 |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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LVLS. However, at this point a decision will be made to determine whether to proceed to a Phase III 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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 31 |