Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Localized Renal Cell Carcinoma (Moonlanding)
A Randomized Phase 2 Trial of Neoadjuvant Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Patients With Localized Renal Cell Carcinoma
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Cristina Suárez, Dr
- Número de teléfono: +34 932543450
- Correo electrónico: csuarez@vhio.net
Ubicaciones de estudio
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Andalusia
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Córdoba, Andalusia, España, 14004
- Hospital Universitario Reina Sofia
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Contacto:
- Mª José Méndez, Dr
- Número de teléfono: +34 957010380
- Correo electrónico: mjosemv@yahoo.es
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Investigador principal:
- Mª José Méndez, Dr
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Aragon
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Zaragoza, Aragon, España, 50009
- Hospital Clínico Universitario Lozano Blesa
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Contacto:
- Julio Lambea, Dr
- Número de teléfono: +34 976765769
- Correo electrónico: juliolambea@yahoo.es
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Investigador principal:
- Julio Lambea, Dr
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Cantabria
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Santander, Cantabria, España, 39008
- Hospital Universitario Marqués de Valdecilla
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Contacto:
- Ignacio Durán, Dr
- Número de teléfono: +34 942315515
- Correo electrónico: ignaciojose.duran@scsalud.es
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Investigador principal:
- Ignacio Durán, Dr
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Catalonia
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Barcelona, Catalonia, España, 08036
- Hospital Clinic de Barcelona
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Contacto:
- Oscar Reig, Dr
- Número de teléfono: +34 932275402
- Correo electrónico: oreig@clinic.cat
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Investigador principal:
- Oscar Reig, Dr
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Barcelona, Catalonia, España, 08035
- Hospital Universitari Vall D Hebron
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Contacto:
- Cristina Suárez, Dr
- Número de teléfono: +34 932543450
- Correo electrónico: csuarez@vhio.net
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Investigador principal:
- Cristina Suárez, Dr
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L'Hospitalet de Llobregat, Catalonia, España, 08908
- Institut Catala D'oncologia
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Contacto:
- Mayra Lizbeth Orrillo, Dr
- Número de teléfono: +34 932607136
- Correo electrónico: mayralizbethorrillo@iconcologia.net
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Investigador principal:
- Mayra Lizbeth Orrillo, Dr
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Sabadell, Catalonia, España, 08208
- Parc Taulí Hospital Universitari
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Contacto:
- Enrique Gallardo, Dr
- Número de teléfono: +34 937240084
- Correo electrónico: egallardo@tauli.cat
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Investigador principal:
- Enrique Gallardo, Dr
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Galicia
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Lugo, Galicia, España, 27003
- Hospital Universitario Lucus Augusti
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Contacto:
- Sergio Vazquez, Dr
- Número de teléfono: +34 982296459
- Correo electrónico: Sergio.Vazquez.Estevez@sergas.es
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Investigador principal:
- Sergio Vazquez, Dr
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Ourense, Galicia, España, 32005
- Complejo Hospitalario Universitario de Ourense
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Contacto:
- Ovidio Fernandez, Dr
- Número de teléfono: +34 986217450
- Correo electrónico: ovidiofernandezcalvo@yahoo.es
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Investigador principal:
- Ovidio Fernandez, Dr
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Madrid
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Madrid, Madrid, España, 28041
- Hospital Universitario 12 de Octubre
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Contacto:
- Guillermo de Velasco, Dr
- Número de teléfono: +34 913908547
- Correo electrónico: gdvelasco.gdv@gmail.com
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Investigador principal:
- Guillermo de Velasco, Dr
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Madrid, Madrid, España, 28034
- Hospital Universitario Ramon y Cajal
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Contacto:
- Javier Molina, Dr
- Número de teléfono: +34 913368897
- Correo electrónico: javier.molinace@gmail.com
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Investigador principal:
- Javier Molina, Dr
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Navarre
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Pamplona, Navarre, España, 31008
- Hospital Universitario de Navarra
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Contacto:
- Nuria Lainez, Dr
- Número de teléfono: +34 848422222
- Correo electrónico: Nuria.lainez.milagro@cfnavarra.es
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Investigador principal:
- Nuria Lainez, Dr
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Principality of Asturias
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Oviedo, Principality of Asturias, España, 33011
- Hospital Universitario Central de Asturias
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Contacto:
- Carlos Alvarez, Dr
- Número de teléfono: +34 985108000
- Correo electrónico: carlos.alvfer@gmail.com
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Investigador principal:
- Carlos Alvarez, Dr
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Valencia
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Valencia, Valencia, España, 46026
- Hospital Universitario y Politécnico La Fe
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Contacto:
- Regina Girones, Dr
- Número de teléfono: +34 961244674
- Correo electrónico: girones_reg@gva.es
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Investigador principal:
- Regina Girones, Dr.
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
Male/female participants who are at least 18 years of age on the day of signing informed consent.
2. Willing to provide written informed consent. They may also provide consent for Future Biomedical Research; however, the participant may participate in the main trial without participating in the Future Biomedical Research.
3. Histologically confirmed diagnosis of RCC with a clear cell component with or without sarcomatoid features. Diagnosis is to be made by the investigator and does not require central histology review.
4. Tumours must be T2 with grade 4, T3, T4, or any T with N1, M0 on radiographic imaging using TNM staging (8th edition)
- T2 is defined as a tumour >7cm but limited to the kidney; grade 4 is per the International Society of Urological Pathology (ISUP) grading.
- T3 is defined as tumour extension into major veins or perinephric tissues, but not into ipsilateral adrenal gland or beyond Gerota's fascia.
- T4 is defined as a tumour involving the ipsilateral adrenal gland or invading beyond Gerota's fascia.
N1 is defined as metastatic involvement of regional lymph nodes. 5. Archival tumour tissue sample or newly obtained core, incisional, or excisional biopsy of a tumour lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
6. Have an Eastern Cooperation Oncology Group (ECOG) Performance Status of 0 to 1.
Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.
7. Have been considered suitable for curative intent surgery (partial or total nephrectomy), as evaluated by a surgeon. 8. Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg.
9. Have adequate organ function as defined in the following table (Table 7). Specimens must be collected within 14 days prior to the start of study intervention.
10.Participants agree to the contraception guidelines outlined in section 5.1.3.2.
11.Participants who are HBsAg positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
Hepatitis B screening tests are not required unless:
Known history of HBV infection As mandated by local health authority 12.Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
Hepatitis C screening tests are not required unless:
Known history of HCV infection As mandated by local health authority 13.HIV-infected participants must have well-controlled HIV on antiretroviral therapy (ART), defined as:
- Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening.
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the lower limit of quantification (LLOQ) (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
- It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
- Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the stud
Exclusion Criteria:
1. Has evidence of metastatic disease on screening imaging. 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents within 3 years prior to randomization.
4. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
Participants with low-risk early-stage prostate cancer either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
5. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. COVID-19 and influenza vaccinations are allowed provided they are not live vaccines 6. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug 8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, and/or lenvatinib, and/or belzutifan.
9. Has active autoimmune disease that has required immunosuppressive systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid).
10.Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease11.Has any of the following:
- A pulse oximeter reading <92% at rest, or
- Requires intermittent supplemental oxygen, or
- Requires chronic supplemental oxygen. 12.Has an active infection requiring systemic intravenous therapy. 13.Has moderate to severe hepatic impairment (Child-Pugh B or C). 14.Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
Note: Hepatitis B and C screening tests are not required unless:
- Known history of HBV and HCV infection
- As mandated by local health authority
15.Has urine protein ≥1 g/24 hours.
- Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
Note: Urine dipstick is the preferred method for testing urinary protein, however, urinalysis may be used if the use of urine dipsticks is not feasible.
16.Has had major surgery within 3 weeks prior to first dose of study interventions.
Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility 17.Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
18.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
19.Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
20.Has had an allogenic tissue/solid organ transplant. 21.Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula22.Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
23.Prolongation of QTcF interval to >480 ms. 24.Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
25.Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
26.Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib 27.Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Cohort A
Neoadjuvant therapy with Pembrolizumab (400mg q6w) + Lenvatinib (20mg daily for 12w) + Belzutifan (120mg daily for 12w).
Followed by nephrectomy and pembrolizumab (400mg q6w for 9 months)
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400mg q6w of Pembrolizumab will be administered before nephrectomy in cohorts A and B
120mg daily for 12w of Belzutifan will be administered before nephrectomy in Cohorts A and B
20mg daily for 12 weeks of lenvatinib will be administered before nephrectomy in Cohort A
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Experimental: Cohort B
Neoadjuvant therapy with Pembrolizumab (400mg q6w) + Belzutifan (120mg daily for 12w).
Followed by nephrectomy and pembrolizumab (400mg q6w for 9 months)
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400mg q6w of Pembrolizumab will be administered before nephrectomy in cohorts A and B
120mg daily for 12w of Belzutifan will be administered before nephrectomy in Cohorts A and B
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Comparador activo: Cohort C
Nephrectomy folloewd by pembrolizumab (400mg q6w for 12 months)
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400mg q6w of Pembrolizumab will be administered before nephrectomy in cohorts A and B
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Response Rate
Periodo de tiempo: At 12 weeks from start of treatment
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Radiographic response defined as a decrease of initial tumour size ≥30% from baseline to week 12 CT scan
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At 12 weeks from start of treatment
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Cristina Suárez, Dr, Hospital Vall d'hebrón
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Neoplasias por tipo histológico
- Neoplasias Glandulares y Epiteliales
- Adenocarcinoma
- Neoplasias Urológicas
- Carcinoma
- Neoplasias Renales
- Carcinoma De Célula Renal
- belzutifan
Otros números de identificación del estudio
- VHIO24002
- 2024-519673-18-00 (Ctis)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .