| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Oncological orthopedic surgery (bone and soft tissue sarcomas in the appendicular skeleton, pelvis and scapular girdle). |
| cirugía ortopédica oncológica (sarcomas óseos y de partes blandas en esqueleto apendicular, pelvis y cintura escapular). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Bone or soft tissue cancer |
| Bone or soft tissue cancer |
|
| 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 | 15.1 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10041299 |
| E.1.2 | Term | Soft tissue sarcomas |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10039498 |
| E.1.2 | Term | Bone sarcomas |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| Demonstrate the superiority of ATX use in combined versus iv and local administration alone |
| Demostrar la superioridad del uso de ATX en administración combinada frente a la vía iv y local aislados |
|
| E.2.2 | Secondary objectives of the trial |
1) Compare local administration versus iv administration of ATX.
2) Determine the number of blood transfusions required in each group
3) Evaluate disease-free survival, relapse-free survival, and distance disease-free survival in each group.
4) To assess the need of stimulating leukocyte colony factors, EPO and days of hospitalization in each group.
5) Evaluate the presence of postoperative hematoma on CT prior to adjuvant radiotherapy among patients with indication of radiotherapy and comparison between groups.
6) Evaluate the safety of ATX use in combined intravenous + local versus intravenous and local administration alone. |
1) Comparar la administración local frente a administración iv de ATX.
2) Determinar el número de trasfusiones sanguínea requeridas en cada grupo
3) Evaluar la supervivencia libre de enfermedad, supervivencia libre de recidiva local y supervivencia libre de enfermedad a distancia en cada grupo.
4) Valorar la necesidad de factores estimuladores de colonias de leucocitos, EPO y días de estancia en cada grupo.
5) Evaluar la presencia de hematoma post-quirúrgico en tomografía previo a radioterapia adyuvante entre los pacientes con indicación de radioterapia y comparación entre los grupos.
6) Evaluar la seguridad del uso de ATX en administración combinada por vía intravenosa + local frente a la administración intravenosa y local aisladas. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Male or female patients older than 12 years.
2) Patients with a diagnosis of bone sarcoma or soft tissue sarcoma of more than 10 cm in their largest diameter, appendicular skeleton, pelvis and scapular girdle.
3) Planned surgical intervention in our center (La Paz University Hospital) with the intention of conservative surgery of the limb by means of extensive tumor resection and reconstruction if necessary for soft tissue and / or bone.
4) Preoperative hemoglobin (at the pre-anesthetic assessment, maximum 30 days prior to inclusion) of at least 11 g / dL.
5) The patient or his / her legal representative (if applicable) has understood the study procedures and signed the informed consent.
6) If participant between 12 and 17 years old, the patient must give his assent to participate in the study. |
1) Pacientes hombres o mujeres mayores de 12 años.
2) Pacientes con diagnóstico de sarcoma óseo o sarcoma de partes blandas de más de 10 cm en su diámetro mayor, en esqueleto apendicular, pelvis y cintura escapular.
3) Intervención quirúrgica planificada en nuestro centro (Hospital Universitario La Paz) con intención de cirugía conservadora del miembro mediante resección amplia tumoral y reconstrucción si esta fuera necesaria de partes blandas y/u ósea.
4) Hemoglobina pre-operatoria (en la valoración pre-anestésica, máximo 30 días previo a la inclusión) de al menos 11 g/dL.
5) El paciente o su representante legal (si aplica) haya entendido los procedimientos del estudio y firmado el consentimiento informado.
6) De tener entre 12 y 17 años, el paciente debe dar su asentimiento para participar en el estudio. |
|
| E.4 | Principal exclusion criteria |
1) Known allergy or contraindication to ATX
2) Sarcomas with preoperative intention other than conservative surgery of the limb by wide resection (low grade soft tissue sarcomas with marginal intention, sarcomas requiring radical resection / amputation or bone sarcomas intended for extended intralesional resection).
3) Radical (amputation) programmed surgery.
4) The patient has any of the following comorbidities:
- Severe ischemic heart disease (Class III and IV of the New Cork Heart Association)
- Patients with history of valvulopathy.
- Patients with a history of obstructive sleep apnea syndrome
- History of severe COPD (grade III, IV)
- History of seizures
- Severe renal dysfunction (Creatinine greater than 2mg / dl in male and 1.8g / dl in women in preoperative analysis, maximum 30 days prior to inclusion)
- Severe hepatic dysfunction (Child-Pugh grade C)
5) Coagulopathy identified in the preoperative period (maximum 30 days prior to inclusion), at least 1 of the following:
- Platelet count less than 40,000 / mm3
- International normalized ratio (INR) greater than 1.4
- Prolonged thromboplastin time (aPTT): greater than 1.4 times normal.
6) History of arterial or venous thromboembolic disease
7) History of hematopoietic, hemorrhagic and thrombogenic blood dyscrasias.
8) Retinopathy (limitation of the visual field and distortion in the perception of color)
9) Women of childbearing age with a positive urine pregnancy test the day before surgery.
10) Female patients who are breastfeeding
11) Male and female patients should agree to use highly effective contraceptive methods from the time of signing informed consent and up to at least 7 days after the completion of the study |
1) Alergia conocida o contraindicación al ATX
2) Sarcomas con intención previa a la cirugía distinta de cirugía conservadora del miembro mediante resección amplia (sarcomas de partes blandas de bajo grado con intención marginal, sarcomas que requieran resección radical/amputación o sarcomas óseos con intención de resección intralesional ampliada).
3) Cirugía radical (amputación) programada.
4) El paciente presenta alguna de las siguientes comorbilidades:
- Cardiopatía isquémica severa (clase III y IV de la New Cork Heart Association)
- Pacientes con antecedente de valvulopatía.
- Pacientes con antecedente de síndrome de apnea obstructiva del sueño
- Antecedentes de EPOC severo (grado III, IV)
- Antecedentes de convulsiones
- Disfunción renal severa (Creatinina mayor de 2mg/dl en hombre y 1,8 g/dl en mujeres en la analítica preoperatoria, máximo 30 días previo a la inclusión)
- Disfunción hepática severa (grado C de Child-Pugh)
5) Coagulopatía identificada en el pre-operatorio (máximo 30 días previo a la inclusión), al menos 1 de las siguientes:
- Recuento plaquetario menor de 40.000/mm3
- Razón internacional normalizada (INR) mayor de 1.4
- Tiempo parcial de tromboplastina (TTPa) prolongado: mayor de 1.4 veces la normal.
6) Antecedentes de enfermedad tromboembólica arterial o venosa
7) Antecedentes de discrasias sanguíneas hematopoyéticas, hemorrágicas y trombogénicas.
8) Retinopatía (limitación del campo visual y distorsión en la percepción del color)
9) Pacientes mujeres en edad fértil con una prueba de embarazo en orina positiva el día previo a la cirugía.
10) Pacientes mujeres que se encuentre en período de lactancia
11) Los pacientes hombres y mujeres deben aceptar usar métodos anticonceptivos altamente eficaces desde el momento de la firma del consentimiento informado y hasta al menos 7 días posterior a la finalización del estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Pérdida de sangre a través del drenaje Drenofast e indirectamente mediante los valores de hemoglobina y hematocrito |
| Loss of blood through Drenofast drainage and indirectly through hemoglobin and hematocrit values |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 24 hours after surgery the milliliters of blood lost with the drenofast and at 24 hours and 5 days by analyzing the hemoglobin and hematocrit values. |
| 24 horas después de la cirugía los mililitros de sangre perdidos con el drenofast y a las 24 horas y 5 días mediante el análisis de los valores de hemoglobina y hematocrito |
|
| E.5.2 | Secondary end point(s) |
• Number of trasfusiones made in each group.
• Assessment of the need for EPO and colony stimulating factors (CSF) of leukocytes.
• Determination of days of hospital stay
• Evaluation of the size of the postoperative hematoma in radiotherapy planning tomography.
• Assessment of adverse events.
• Evaluation of surgical complications
• Assessment of disease-free survival and local events in long-term follow-up through imaging tests. |
• Número de trasfusiones realizadas en cada grupo.
• Valoración de la necesidad de EPO y factores estimuladores de colonias (CSF) de leucocitos.
• Determinación de días de estancia hospitalaria
• Valoración del tamaño del hematoma postquirúrgico en tomografía de planificación de radioterapia.
• Evaluación de los acontecimientos adversos.
• Valoración de complicaciones quirúrgicas
• Valoración de la supervivencia libre de enfermedad y eventos locales en el seguimiento a largo plazo a través de pruebas de imágenes. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| after intervention |
| Tras la intervención |
|
| 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 | 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 | Yes |
| 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 | 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 | 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 | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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