E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Triple Negative Breast Cancer |
Cáncer de Mama Avanzado Triple Negativo |
|
E.1.1.1 | Medical condition in easily understood language |
Breast Cancer not dependent on hormones |
El cáncer de mama no depende de las hormonas |
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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 | LLT |
E.1.2 | Classification code | 10072737 |
E.1.2 | Term | Advanced breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To assess the anti-tumor activity of MCS110 combined with carboplatin/gemcitabine (carbo/gem) compared to carbo/gem alone. |
El objetivo principal es evaluar la actividad antitumoral de MCS110 en combinación con carbo/gem comparado con carbo/gem en monoterapia en pacientes adultas con CMTN. |
|
E.2.2 | Secondary objectives of the trial |
1. Characterize the safety and tolerability of MCS110 given in combination with carbo/gem. 2. Characterize PK of MCS110 when combined with carbo/gem. 3. Characterize PK of carbo and gem in the presence and absence of MCS110. 4. Characterize PD effect of MCS110 when combined with carbo/gem 5. To assess the anti-tumor activity of MCS110 given in combination with carbo/gem as measured by additional efficacy measures. |
- Determinar la seguridad y la tolerabilidad de MCS110 administrado en combinación con carbo/gem - Determinar la PK de MCS110 en combinación con carbo/gem. - Determinar la PK de carbo/gem en presencia y ausencia de MCS110. - Determinar el efecto PD de MCS110 en combinación con carbo/gem. - Evaluar la actividad antitumoral de MCS110 administrado en combinación con carbo/gem mediante medidas adicionales de eficacia. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult women (? 18 years of age) with advanced TNBC. - Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) BC by local laboratory testing, based on last available tumor tissue. - ER/PgR negativity to follow local guidelines - If IHC HER2 2+, a negative FISH test is required A pre-treatment tumor biopsy demonstrating high TAM content as assessed per the central laboratory (approximately 15% of TAMs or above). - Patients must have: - At least one measurable lesion per RECIST 1.1. (Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an identifiable soft tissue component that meets the measurability criteria) or - Bone lesions: non-measurable lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above. Patients with only non-measurable lesions (e.g. pleural effusion, ascites) and no lytic or mixed bone lesions are not eligible.
Other inclusion criteria may apply |
- Mujeres adultas (? 18 años de edad) con CMTN avanzado. - Confirmación histológica o citológica de cáncer de mama con receptor de estrógeno negativo (RE-), receptor de progesterona negativo (RP-) y receptor del factor de crecimiento epidérmico humano 2 negativo (HER2-) mediante pruebas analíticas locales basadas en el último tejido tumoral disponible. * Negatividad de RE/RP según las directrices locales. * En caso de IHC HER-2 2+, se requiere una prueba FISH negativa. - Biopsia del tumor previa al tratamiento que demuestre un alto contenido de TAM según la evaluación del laboratorio central (aproximadamente un 15% de TAM o superior). - Las pacientes deben tener: Al menos una lesión medible según RECIST 1.1. (Nota: las lesiones medibles incluyen lesiones óseas líticas o mixtas (líticas + blásticas) con un componente de tejido blando identificable que cumpla los criterios de medición). |
|
E.4 | Principal exclusion criteria |
- Prior chemotherapy for advanced BC. Previous adjuvant/neoadjuvant chemotherapy is allowed. - Therapy for underlying malignancy within 2 weeks prior to start of study treatment: - Chemotherapy, biologic therapy (antibodies and biologically targeted small molecules) - Radiotherapy - Major surgery - Patients receiving concomitant immunosuppressive agents or chronic corticosteroids (?10 mg of prednisone or equivalent) at the time of first dose of study drug. - Known history of human immunodeficiency virus or active infection with hepatitis virus or any uncontrolled active systemic infection. - Patients with the following laboratory values during screening and on Day 1 pre-dose: - Absolute Neutrophil Count (ANC) < 1.0x109/L - Hemoglobin < 9 g/dL - Platelets < 100x109/L - Serum creatinine > 1.5 x ULN - Serum total bilirubin > 1.5 x ULN - AST/SGOT and ALT/SGPT > 3.0 x ULN
Other exclusion criteria may apply |
- Tratamiento previo con quimioterapia para CM avanzado. Está permitido tratamiento previo con quimioterapia adyuvante/neoadyuvante. - Tratamiento contra la enfermedad maligna subyacente en las 2 semanas anteriores al inicio del tratamiento del estudio: * Quimioterapia, terapia biológica (anticuerpos y moléculas pequeñas dirigidas biológicamente). * Radioterapia. * Cirugía mayor. - Pacientes que reciben fármacos inmunosupresores concomitantes o corticosteroides crónicos (prednisona ?10 mg o equivalente) en el momento de la administración de la primera dosis del estudio - Enfermedad cardiovascular clínicamente significativa como arritmias sintomáticas o no controladas, insuficiencia cardíaca congestiva o infarto de miocardio durante los 6 meses anteriores a la selección. - Antecedentes conocidos del virus de la inmunodeficiencia humana, infección activa por el virus de la hepatitis o cualquier infección sistémica activa no controlada. - Pacientes que durante la selección y el día 1 antes de la dosis presenten los valores de laboratorio siguientes: * Recuento absoluto de neutrófilos (RAN) < 1,0x109/l. * Hemoglobina < 9 g/dl. * Plaquetas < 100x109/l. * Creatinina sérica > 1,5 x LSN. * Bilirrubina sérica total > 1,5 x LSN. * AST/SGOT y ALT/SGPT > 3,0 x LSN. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PFS as per RECIST v1.1 (by local investigator assessment) |
SLP según RECIST v1.1 (determinada por la evaluación del investigador local). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor evaluation at sreening and then every six weeeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8). |
Evaluación del tumor en sreening y luego cada seis semanas hasta el final del ciclo 8. En lo sucesivo, cada 9 semanas (después del ciclo 8). |
|
E.5.2 | Secondary end point(s) |
1. Safety: adverse event (AEs), serious adverse events (SAEs) Tolerability: Dose interruptions, reductions and dose intensity 2. Serum concentration of free MCS110 and derived PK parameters 3. Plasma concentration of carboplatin, gemcitabine and dFdU (the primary metabolite of gem), and derived PK parameters 4. Total CSF-I circulating levels, serum CTX-I and circulating monocytes in blood. TAM and TIL content in pre- and post-dose tumor biopsies 5. Tumor response per RECIST v1.1 (by local investigator assessment): Overall Response Rate (ORR), Duration of Response (DOR), Clinical Benefit Rate (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ? 6 months) and Overall Survival (OS). |
Seguridad: acontecimientos adversos (AA), acontecimientos adversos graves (AAG). Tolerabilidad: Interrupciones, reducciones e intensidad de la dosis. Concentración de MCS110 libre en suero y parámetros PK derivados Concentración de carboplatino, gemcitabina y dFdU (el metabolito principal de gem) en plasma y parámetros PK derivados. Niveles circulantes totales del CSF-1, CTX-1 en suero y monocitos circulantes en sangre. Contenido de TAM y TIL en biopsias del tumor antes y después de la dosis. Respuesta del tumor según RECIST v1.1 (determinada por la evaluación del investigador local): tasa de respuesta global (TRG), duración de la respuesta (DR), tasa de beneficio clínico (respuesta completa (RC) + respuesta parcial (RP) + enfermedad estable (EE) ? 6 meses) y supervivencia global (SG). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Continuously 2. Please refer to protocol section 7 3. Please refer to protocol section 7 4. Please refer to protocol section 7 5. ORR:Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8). DOR: Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8). Clinical benefit rate: Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8). Overall survival: 4, 6, 9, 12 and 18 months |
1. continuamente 2. Por favor consulte la sección de protocolo 7 3. Por favor, consulte la sección de protocolo 7 4. Por favor, consulte la sección de protocolo 7 5. TRG: evaluación del tumor en la selección y luego cada seis semanas hasta el final del ciclo 8. sucesivo, cada 9 semanas (después del ciclo 8). DOR: evaluación del tumor en la selección y luego cada seis semanas hasta el final del ciclo 8. sucesivo, cada 9 semanas (después del ciclo 8). Tasa de beneficio clínico: Tumor de evaluación en la selección y luego cada seis semanas hasta el final del ciclo 8. sucesivo, cada 9 semanas (después del ciclo 8). La supervivencia global: 4, 6, 9, 12 y 18 meses |
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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 | Yes |
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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
carboplatino, gemcitabina |
carboplatin , gemcitabine |
|
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Czech Republic |
France |
Germany |
Hong Kong |
Israel |
Italy |
Korea, Democratic People's Republic of |
Singapore |
Spain |
Taiwan |
Turkey |
United States |
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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
|
End of study will be upon completion of survival follow-up or if the study is terminated early.
The survival follow-up will end once at least 80% of patients enrolled have died, discontinued, withdrawn consent, been lost to follow-up or all the patients have completed the survival follow-up period (18 months after the first dose of treatment), whichever occurs earlier. |
El fin de estudio tendrá lugar una vez completado el seguimiento de la supervivencia o si el estudio finaliza prematuramente. El seguimiento de la supervivencia finalizará cuando al menos el 80% de las pacientes incluidas hayan fallecido, se hayan retirado, hayan revocado su consentimiento, sean pérdida de seguimiento o cuando todas las pacientes hayan completado el periodo de seguimiento de la supervivencia (18 meses después de la primera dosis del tratamiento), aquello que ocurra antes. |
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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 | |
E.8.9.1 | In the Member State concerned months | 34 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 34 |