E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lynch Syndrome |
Síndrome de Lynch |
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E.1.1.1 | Medical condition in easily understood language |
An inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, endometrium and also other cancers. |
Trastorno hereditario que aumenta el riesgo de muchos tipos de cáncer, en particular el cáncer de colon (intestino grueso) y recto, endometrio y también otros cánceres. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051981 |
E.1.2 | Term | Lynch syndrome |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether the cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer incidence rates annually from 5 years in people who took 100mg, 300mg or 600mg enteric coated aspirin for at least 2 years. |
Determinar si las propiedades preventivas del cáncer de la aspirina con cubierta entérica en el síndrome de Lynch son sensibles a la dosis al comparar las tasas de incidencia acumuladas de cáncer a los 5 años en personas que tomaron 100 mg, 300 mg o 600 mg de aspirina con cubierta entérica durante al menos 2 años. |
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E.2.2 | Secondary objectives of the trial |
• Compare overall primary colorectal cancers in the three treatment groups. • Compare overall primary endometrial cancers in the three treatment groups. • Compare overall cancers of all types,in the three treatment groups. • Compare the burden of adverse events in three treatment groups. |
• Comparar la totalidad de cánceres colorrectales primarios en los tres grupos de tratamiento. • Comparar la totalidad de cánceres endometriales primarios en los tres grupos de tratamiento. • Comparar la totalidad de cánceres de cualquier tipo, en los tres grupos de tratamiento. • Comparar la cantidad y gravedad de eventos adversos en tres grupos de tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age over 18. 2. Confirmed germline pathological variant in one of the mismatch repair genes; MSH2, MLH1, PMS2 or MSH6 or a 3’ EPCAM deletion associated with MSH2 silencing or be a carriers of a constitutional epimutation manifesting a classic Lynch syndrome phenotype. 3. Able to swallow tablets. 4. Willing to complete the CaPP3 consent process as described in the patient information sheet. |
1. Edad mayor de 18 años. 2. Variante patológica confirmada de la línea germinal en uno de los genes reparadores de desemparejamientos; MSH2, MLH1, PMS2 o MSH6 o una deleción 3 'EPCAM asociada con el silenciamiento de MSH2 o ser portadores de una epimutación constitucional que manifiesta un fenotipo de síndrome de Lynch clásico. 3. Capaz de tragar las tabletas. 4. Dispuesto a completar el proceso de consentimiento tal como se describe en la hoja de información del paciente. |
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E.4 | Principal exclusion criteria |
1. Regular use of an oral non-steroidal anti-inflammatory agent on long-term basis. Regular is defined as > 3 doses per week, for more than 3 months in the last 3 years. 2. Previous regular use of aspirin at a daily dose of 150mg or less does not exclude enrolment but duration and quantity need to be documented in detail. More than 3 months use of > 150mg or more per day in the last 3 years is an exclusión. 3. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma. 4. Existing clinically significant liver impairment. 5. Existing renal failure defined as creatinine clearance <10ml/min 6. Confirmed active peptic ulcer disease within the previous three months. 7. Known bleeding diathesis or concomitant anticoagulant therapy. 8. Inability to comply with study procedures and agents. 9. Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years. 10. Women who are breastfeeding. 11. Any significant medical illness that would interfere with study participation. (If hypertension is discovered, the participant should be advised to have this treated before commencing trial medication). 12. Bi-allelic Mismatch Repair Deficiency BMMRD (also known as Constitutional Mismatch Repair Deficiency). |
1. Uso regular de un agente antiinflamatorio no esteroideo oral a largo plazo. Regular se define como > 3 dosis por semana, durante más de 3 meses en los últimos 3 años. 2. El tratamiento previo con aspirina a una dosis diaria de 150 mg o menos no es criterio de exclusión, pero la duración y la cantidad deben documentarse en detalle. El uso de más de 3 meses de > 150 mg al día en los últimos 3 años es criterio de exclusión. 3. Intolerancia o hipersensibilidad conocida a la aspirina conocida, incluido el asma sensible a la aspirina. 4. Existencia de insuficiencia hepática clínicamente significativa. 5. Existencia de insuficiencia renal definida como aclaramiento de creatinina <10 ml / min 6. Confirmación de enfermedad de úlcera péptica activa en los últimos tres meses. 7. Diátesis hemorrágica conocida o terapia anticoagulante concomitante. 8. Incapacidad para cumplir con los procedimientos y tratamientos del estudio. 9. Mujeres embarazadas o que planean un embarazo dentro de los siguientes dos años. 10. Mujeres en periodo de lactancia. 11. Cualquier enfermedad médica significativa que pueda interferir con la participación en el estudio. (Si se diagnostica hipertensión, se le debe recomendar al participante que reciba tratamiento para ello antes de comenzar el tratamiento del ensayo). 12. Deficiencia de reparación de desemparejamiento bialélica BMMRD (también conocida como deficiencia de reparación de apareamiento constitucional). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of new primary mismatch repair deficient cancers (“Lynch syndrome cancers”) at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. |
Número de nuevos "cánceres del síndrome de Lynch" a los 5 años en pacientes que reciben tratamiento preventivo durante un mínimo de 2 años. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Five years after last recruit enters trial |
Cinco años después de la inclusión del último paciente |
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E.5.2 | Secondary end point(s) |
• The number of new colorectal cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. • The number of new endometrial cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. • The number of new cancers of all types at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. |
• Número de nuevos cánceres colorrectales a los 5 años que se desarrollan en los participantes que permanecen en tratamiento prescrito durante un mínimo de 2 años. • Número de nuevos cánceres endometriales a los 5 años que se desarrollan en participantes que permanecen bajo tratamiento prescrito durante un mínimo de 2 años. • Número de cánceres nuevos de todos los tipos a los 5 años que se desarrollan en los participantes que permanecen en tratamiento prescrito durante un mínimo de 2 años. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• The number of new colorectal cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. • The number of new endometrial cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. • The number of new cancers of all types at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years. |
• Número de nuevos cánceres colorrectales a los 5 años que se desarrollan en los participantes que permanecen en tratamiento prescrito durante un mínimo de 2 años. • Número de nuevos cánceres endometriales a los 5 años que se desarrollan en participantes que permanecen bajo tratamiento prescrito durante un mínimo de 2 años. • Número de cánceres nuevos de todos los tipos a los 5 años que se desarrollan en los participantes que permanecen en tratamiento prescrito durante un mínimo de 2 años. |
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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 | No |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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End of study is defined as five years from randomisation of the last patient |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |