E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Conventional chondrosarcoma Myxoid liposarcoma with PIK3CA mutation or PTEN loss Mesenchymal or dedifferentiated chondrosarcoma |
Condrosarcoma convencional Liposarcoma mixoide con mutación PIK3CA o ausencia de PTEN Condrosarcoma mesenquimal o desdiferenciado |
|
E.1.1.1 | Medical condition in easily understood language |
Chondrosarcoma Myxoid liposarcoma |
Condrosarcoma Liposarcoma mixoide |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
To evaluate the treatment efficiency by growth modulation index |
Evaluar la eficiencia del tratamiento con el índice de crecimiento modulado |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of the sirolimus and cyclophosphamide combination - To determine the median progression free survival after start of treatment till disease progression - To determine the overall survival after start of treatment till death |
- Evaluar la seguridad y la tolerabilidad de la combinación de sirolimus y ciclofosfamida. - Determinar la mediana de supervivencia libre de progresión desde el inicio del tratamiento hasta la progresión de la enfermedad - Determinar la supervivencia global desde el inicio del tratamiento hasta la muerte. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Pathologically proven conventional chondrosarcoma - Or pathologically proven myxoid liposarcoma with PIK3CA mutation or PTEN loss - Or pathologically proven mesenchymal or dedifferentiated chondrosarcoma - Patients of 18 years and up - Documented radiographic progression of disease according to RECIST 1.1 criteria in last 6 months - Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 80 x 109/L) - Availability of archival tumor material for central review - Written signed informed consent - Ability to adhere to the study visits and all protocol requirements |
- Condrosarcoma convencional confirmado por anatomía patológica. - O liposarcoma mixoide con mutación PIK3CA o ausencia de PTEN conformado por anatomía patológica. - O Condrosarcoma mesenquimal o desdiferenciado confirmado por anatomía patológica. - Pacientes con 18 años o más. - Progresión radiológica documentada de acuerdo a los criterios RECIST 1.1 en los últimos 6 meses. |
|
E.4 | Principal exclusion criteria |
- Previously treated with an mTOR inhibitor - Known to be allergic to cyclophosphamide - Life expectancy of less than 3 months - No measurable lesions according to RECIST 1.1 - ECOG Performance status >2 - Major surgery less than 4 weeks prior to start of treatment - Known human immunodeficiency virus (HIV) positivity - A decreased renal function with calculated GFR < 30 ml/min - Systemic anti-cancer therapy within 28 days prior to the first dose of study drug , or radiotherapy to an index (or target) lesion within 21 days prior to the first dose of study drug - Pregnant or lactating women - Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localised cured prostate and cervical cancer |
- Previamente tratado con inhibidor de mTOR. - Alergia conocida a ciclofosfamida - Esperanza de vida menor a 3 meses. - Lesión no medible por los criterios RECIST 1.1 - Estado ECOG>2 - Cirugía mayor en los últimos 4 meses antes de iniciar el tratameinto. - Virus de la inmunodeficiencia humana diagnosticado. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to progression during sirolimus/cyclofosfamide treatment (TTP2) divided by time to progression before start of this treatment TTP1 (=growth modulation index) |
Tiempo a la progresión durante el tratamiento de sirolimus/ciclofosfamida (TTP2) entre el tiempo a la progresión del tratameinto anterior (TTP1) = indíce de modulación de crecimeinto) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be evaluated with CT-scan every 8 weeks |
Los pacientes serán evaluados con un TAC cada 8 semanas. |
|
E.5.2 | Secondary end point(s) |
- Translational exploratory tumour pharmacodynamic analysis - Toxicity according to CTC version 4.0 - Objective response defined as a partial or complete response occurring after start of treatment according to RECIST1.1 - Time to progression according to RECIST 1.1 - Overall survival from start of treatment until death |
- Análisis farmacodinámico de la exploración traslacional tumoral. - Toxicidad de acuerdo a la guía CTC versión 4.0 - Respuesta objetiva definida como respuesta parcial o completa ocurrida tras el inicio del tratamiento de acuerdo a los criterios RECIST 1.1 - Supervivencia global desde el inicio del tratamiento hasta el exitus. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. every 4 weeks on outpartient clinic visit 2. every 8 weeks with CT-scan |
1. Cada 4 semanas con visita clínica 2. Cada 8 semanas con TAC |
|
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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | No |
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 | 6 |
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 | 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
|
LVLS |
Ultima visita del último paciente |
|
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 | |
E.8.9.2 | In all countries concerned by the trial years | 2 |