Inmunoterapia (Toripalimab) para prevenir la recurrencia después de la cirugía para reparación de desajuste deficiente en estadio IIB, IIC o III Cáncer de colon
Un ensayo de fase II de toripalimab adyuvante en cáncer de colon localizado de alto riesgo con deficiencia de reparación de desajustes
This phase II trial tests how well immunotherapy (toripalimab) works for reducing the risk of cancer recurrence after surgery in patients with mismatch repair deficient stage IIB, IIC, or III colon cancer.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
PRIMARY OBJECTIVE:
I. Evaluate the efficacy of adjuvant toripalimab in patients with resected stage IIB, IIC, and III mismatch repair deficient (dMMR) colon cancer by measuring 3-year disease-free survival.
SECONDARY OBJECTIVES:
I. Define the immune related toxicity profile of toripalimab in the adjuvant setting.
II. Further evaluate the efficacy of adjuvant toripalimab specifically by measuring 3-year relapse free survival (RFS), 5-year disease free survival (DFS), and 5-year overall survival.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To explore immune, ctDNA, and omic markers associated with clinical efficacy (DFS).
II. To assess patient reported outcomes (PRO) and health related quality of life (QoL).
OUTLINE:
Eligible consenting participants will receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months until 5 years post-resection. After completion of study medication, participants undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. Patient reported outcomes and quality of life will also be assessed with questionnaires.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Oluwadunni E. Emiloju, MBBS, MS
- Número de teléfono: 404-778-1900
- Correo electrónico: oluwadunni.eunice.emiloju@emory.edu
Copia de seguridad de contactos de estudio
- Nombre: Olatunji B. Alese, MD, FASCO
- Correo electrónico: olatunji.alese@emory.edu
Ubicaciones de estudio
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Reclutamiento
- Emory University Hospital/Winship Cancer Institute
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Investigador principal:
- Oluwadunni E. Emiloju, MBBS, MS
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Contacto:
- Tyler Whitfield
- Número de teléfono: 404-778-1900
- Correo electrónico: tyler.stephen.whitfield@emory.edu
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Atlanta, Georgia, Estados Unidos, 30308
- Reclutamiento
- Emory University Hospital Midtown
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Contacto:
- Jalpa Patel
- Correo electrónico: jalpa.r.patel@emory.edu
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Investigador principal:
- Oluwadunni E. Emiloju, MBBS, MS
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Atlanta, Georgia, Estados Unidos, 30342
- Reclutamiento
- Emory Saint Joseph's Hospital
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Investigador principal:
- Oluwadunni E. Emiloju, MBBS, MS
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Contacto:
- Ainsley Hymel
- Correo electrónico: ainsley.hymel@emory.edu
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Atlanta, Georgia, Estados Unidos, 30033
- Reclutamiento
- Emory Decatur Hospital
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Investigador principal:
- Oluwadunni Emiloju
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Contacto:
- Kathleen Coleman
- Número de teléfono: 404-778-1900
- Correo electrónico: kmcole5@emory.edu
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Johns Creek, Georgia, Estados Unidos, 30097
- Reclutamiento
- Emory Johns Creek Hospital
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Investigador principal:
- Oluwadunni E. Emiloju, MBBS, MS
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Contacto:
- Hafsa Ahmed
- Correo electrónico: hafsa.maheen.ahmed@emory.edu
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Patients with resected pathologic stage IIB, IIC and III dMMR colon cancer (American Joint Committee on Cancer [AJCC] 8)
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Deficient mismatch repair (MMR) by immunohistochemistry or microsatellite instability (MSI-H) by polymerase chain reaction (PCR) or next generation sequencing (NGS)
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Complete (R0) resection of pathologic stage IIB, IIC and III dMMR colon cancer 4 to 12 weeks prior to first dose of study drug
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Available tissue sample from surgical specimen
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Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
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Absolute neutrophil count (ANC) ≥ 1,000 /mcL
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Platelets ≥ 75,000 / mcL
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Hemoglobin ≥ 9 g/dL or ≥ 5.0 mmol/L
- Transfusion is allowed to obtain an adequate hemoglobin level
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Creatinine ≤ 1.5 x upper limit of normal (ULN) or measured or calculated creatinine clearance ≥ 40 mL/min for patient with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
- Creatinine clearance should be calculated per institutional standard
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Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN
- Patients with previously diagnosed Gilbert syndrome can have total bilirubin < 3.0 mg/dL
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Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x ULN
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Alkaline phosphatase ≤ 3 x ULN
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Signed informed consent
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Patients at least 18 years of age
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Colonoscopy should be performed before surgery and if synchronous colon cancers are present, both must have deficient MMR and both must have undergone complete resection for patient to be eligible. If colonoscopy was not done pre-operatively, the patient may still be eligible if all other inclusion criteria are met. It should however be performed within 6 months after initial colon resection surgery
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Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP are women younger than 55 years (yrs) of age excluding those who are surgically unable to get pregnant due to prior hysterectomy and or bilateral salpingo-oophorectomy
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Patients of childbearing / reproductive potential should use adequate birth control methods, as defined by the investigator, during the study treatment period and for a period of 90 days after the last dose of study drug. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard
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Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 90 days after the last dose of study drug
Exclusion Criteria:
- Neoadjuvant treatment for dMMR colon cancer
- Presence of metastatic dMMR colon cancer
- Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of adverse events
- Uncontrolled psychiatric illness or psychological condition potentially hampering compliance with the study protocol and follow-up schedule
- History of pneumonitis requiring treatment with steroids, or history of interstitial lung disease
- History of prior malignancy other than the cancer under study, that is progressing or has required active treatment within the past 3 years. Exceptions include adequately treated basal cell or squamous cell carcinoma of skin, superficial bladder cancer, in situ cervical cancer, in situ breast cancer, other in situ cancers, prostate cancer with a Gleason score ≤6 that does not need therapy or other local tumors that are considered cured.
- Autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, diabetes mellitus type 1, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, controlled psoriasis or resolved childhood asthma/atopy not requiring systemic treatment can be enrolled
- Active hepatitis B or hepatitis C
- Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, nasal seasonal flu, H1N1 flu, rabies, Bacille Calmette Guerin (BCG) and typhoid vaccine
- Prior treatment with any immune checkpoint inhibitor
- Current pregnancy or breastfeeding
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Treatment (toripalimab)
Eligible consenting participants receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. Following this, patients undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. For patients who have a recurrence, a biopsy will be performed at the time of recurrence. |
Undergo CT
Otros nombres:
Ancillary studies Undergo biopsy
Otros nombres:
Undergo collection of blood samples
Otros nombres:
Undergo colonoscopy Given IV
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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3-year Disease free survival (DFS)
Periodo de tiempo: Time between the date of registration and the first date of documented recurrence or death due to any cause assessed up to 3 years
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Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 3 years |
Time between the date of registration and the first date of documented recurrence or death due to any cause assessed up to 3 years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Incidence of treatment-related adverse events
Periodo de tiempo: Up to 5 years
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Safety will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Treatment-related adverse events (defined as potentially, probably and definitely) will be summarized in preferred term by system organ class and listed on an individual subject basis at patient level. Immune-related adverse events will also be tabulated. |
Up to 5 years
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3-year Relapse free survival (RFS)
Periodo de tiempo: Time between the date of registration and the first date of documented disease recurrence assessed up to 3 years.
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Time between the date of registration and the first date of documented disease recurrence, assessed at 3 years |
Time between the date of registration and the first date of documented disease recurrence assessed up to 3 years.
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5-year DFS
Periodo de tiempo: Time between the date of registration and the first date of documented recurrence, or death due to any cause assessed up to 5 years
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Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 5 years. |
Time between the date of registration and the first date of documented recurrence, or death due to any cause assessed up to 5 years
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Colon cancer specific survival (CCSC)
Periodo de tiempo: Time between the date of registration and the date of death due to colon cancer, assessed up to 5 years
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CCSC is the time between the date of registration and the date of death due to colon cancer, assessed up to 5 years |
Time between the date of registration and the date of death due to colon cancer, assessed up to 5 years
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Overall survival (OS)
Periodo de tiempo: Time between the date of registration and the date of death due to any cause, assessed up to 5 years
|
Time between the date of registration and the date of death due to any cause. |
Time between the date of registration and the date of death due to any cause, assessed up to 5 years
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Oluwadunni E. Emiloju, MBBS, MS, Emory University Hospital/Winship Cancer Institute
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades intestinales
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Neoplasias colorrectales
- Neoplasias Intestinales
- Enfermedades del Colon
- Neoplasias colónicas
- Técnicas de investigación
- Técnicas de laboratorio clínico
- Técnicas y procedimientos de diagnóstico
- Diagnóstico
- Procedimientos quirúrgicos, operativo
- Procedimientos quirúrgicos mínimamente invasivos
- Técnicas citológicas
- Citodiagnóstico
- Técnicas de diagnóstico, quirúrgico
- Endoscopia, gastrointestinal
- Endoscopia, sistema digestivo
- Técnicas de diagnóstico, sistema digestivo
- Endoscopia
- Procedimientos quirúrgicos del sistema digestivo
- Biopsia
- Manejo de muestras
- Colonoscopia
- toripalimab
Otros números de identificación del estudio
- STUDY00008833
- P30CA138292 (Subvención/contrato del NIH de EE. UU.)
- STUDY00008833 (Otro identificador: Emory University Hospital/Winship Cancer Institute)
- NCI-2025-05423 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- WINSHIP6483-24 (Otro identificador: Emory University Hospital/Winship Cancer Institute)
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.
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