A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation
A Multi-center, Open-label Phase Ib/II Study Exploring the Safety/Tolerability, Pharmacokinetics, and Efficacy of GFH276 in Combination With Cetuximab or Chemotherapy in the Treatment of Patients With Advanced Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation
A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation
Descripción general del estudio
Estado
Descripción detallada
This is an open-label, multicenter Phase Ib/II clinical trial to evaluate the safety, tolerability, and preliminary anti-tumor efficacy of oral GFH276 in combination with cetuximab or standard chemotherapy in adult patients with locally advanced or metastatic RAS-mutated solid tumors and pancreatic ductal adenocarcinoma (PDAC).
Participants will be enrolled into three treatment arms with different combination regimens.
In the Phase Ib stage, dose escalation of GFH276 will be performed in each combination arm to identify the optimal recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, Phase II expansion cohorts will enroll eligible patients to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Bai Li
- Número de teléfono: 18201333260
- Correo electrónico: lbai@genfleet.com
Copia de seguridad de contactos de estudio
- Nombre: Zhang Pingping
- Número de teléfono: 18758558734
- Correo electrónico: ppzhang@genfleet.com
Ubicaciones de estudio
-
-
New South Wales
-
Concord, New South Wales, Australia, 2139
- Aún no reclutando
- Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District
-
Contacto:
- Kim Tam B Bui, MBBS
- Número de teléfono: 0297674425
- Correo electrónico: Tam.Bui@health.nsw.gov.au
-
North Ryde, New South Wales, Australia, 2109
- Reclutamiento
- Macquarie University / Clinical Trials Unit
-
Contacto:
- PhD
-
Contacto:
- Andrew Parsonson, PhD
- Número de teléfono: 0298122956
- Correo electrónico: andrew.parsonson@mqhealth.org.au
-
-
South Australia
-
Woodville South, South Australia, Australia, 5011
- Aún no reclutando
- The Queen Elizabeth Hospital
-
Contacto:
- Timothy Price, MBBS
- Número de teléfono: 0882227096
- Correo electrónico: timothy.price@sa.gov.au
-
-
Victoria
-
Clayton, Victoria, Australia, 3168
- Reclutamiento
- Monash Health (Monash Medical Centre)
-
Contacto:
- David Lau, PhD
- Número de teléfono: 0385722392
- Correo electrónico: David.Lau@monashhealth.org
-
Epping, Victoria, Australia, 3076
- Aún no reclutando
- Northern Health
-
Contacto:
- Belinda Lee, MBBS
- Número de teléfono: 0384058000
- Correo electrónico: Belinda.Lee@nh.org.au
-
Frankston, Victoria, Australia, 3199
- Reclutamiento
- PASO Medical
-
Contacto:
- Vinod Ganju, MBBS
- Número de teléfono: 0397815244
- Correo electrónico: vg@paso.com.au
-
-
-
-
Beijing Municipality
-
Beijing, Beijing Municipality, Porcelana, 100730
- Reclutamiento
- Peking Union Medical College Hospital
-
Contacto:
- Chunmei Bai, MD
-
-
Guangdong
-
Guangzhou, Guangdong, Porcelana, 510120
- Reclutamiento
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University
-
Contacto:
- Zhihua Li, MD
-
-
Heilongjiang
-
Harbin, Heilongjiang, Porcelana, 150081
- Aún no reclutando
- The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University
-
Contacto:
- Guangyu Wang, MD
-
-
Henan
-
Zhengzhou, Henan, Porcelana, 450052
- Reclutamiento
- The First Affiliated Hospital of Zhengzhou University
-
Contacto:
- Hong Zong, MD
-
-
Hubei
-
Wuhan, Hubei, Porcelana, 430022
- Aún no reclutando
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
-
Contacto:
- Heshui Wu, MD
-
-
Liaoning
-
Shenyang, Liaoning, Porcelana, 110001
- Aún no reclutando
- The First Affiliated Hospital of China Medical University
-
Contacto:
- Xiujuan Qu, MD
-
-
Shaanxi
-
Xi'an, Shaanxi, Porcelana, 710061
- Aún no reclutando
- The First Affiliated Hospital of Xi'an Jiaotong University
-
Contacto:
- Yinying Wu, MD
-
-
Shandong
-
Jinan, Shandong, Porcelana, 250117
- Reclutamiento
- Shandong First Medical University Affiliated Tumor Hospital
-
Contacto:
- Shuqin Ni, MD
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, Porcelana, 200032
- Reclutamiento
- Fudan University Shanghai Cancer Center
-
Contacto:
- Xianjun Yu, MD
- Número de teléfono: 13801669875
- Correo electrónico: yuxianjun@fudanpci.org
-
-
Sichuan
-
Chengdu, Sichuan, Porcelana, 610041
- Reclutamiento
- West China Hospital of Sichuan University
-
Contacto:
- Xuelei Ma, MD
-
-
Zhejiang
-
Hangzhou, Zhejiang, Porcelana, 310016
- Reclutamiento
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
-
Contacto:
- Da Li, MD
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Age ≥ 18 years
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor and PDAC with RAS mutation or KRAS amplification
- At least one measurable lesion according to RECIST v1.1
- ECOG performance status 0 or 1
- Life expectancy > 3 months
- Adequate organ function
- Willing to provide written informed consent
- Fertile participants must use effective contraception
Exclusion Criteria:
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- For participants with known concomitant second oncodriver for PDAC or for solid tumors.
- With active infection (HIV, HBV, HCV, syphilis)
- The presence of clinical or radiological evidence of intestinal obstruction.
- Prior anticancer therapy within 28 days or 5 half-lives
- Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months
- Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- History of central nervous system (CNS)disease
- Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Arm A: GFH276 + Cetuximab
GFH276 once daily; cetuximab 500 mg/m² intravenous infusion every 2 weeks. |
Oral GFH276 administered once daily in combination with other study drugs. Intravenous cetuximab at a dose of 500 mg/m² |
|
Experimental: Arm B: GFH276 + AG
GFH276 once daily; nab-paclitaxel 125 mg/m² + gemcitabine 1000 mg/m² (AG regimen); 4-week cycle (D1, D8, D15) or 3-week cycle (D1, D8) in China |
Oral GFH276 administered once daily in combination with other study drugs. Intravenous nab-paclitaxel at a dose of 125 mg/m². Intravenous Gemcitabine at a dose of 1000 mg/m². |
|
Experimental: Arm C: GFH276 + mFOLFIRINOX
GFH276 once daily; mFOLFIRINOX :Fluorouracil 2400 mg/m²(46 h), Leucovorin 400 mg/m², Irinotecan 150 mg/m², Oxaliplatin 85 mg/m², IV D1, every 2 weeks . The mFOLFIRINOX regimen may be administered per the above dosage, or in accordance with national or institutional guidelines. |
Oral GFH276 administered once daily in combination with other study drugs. Intravenous Fluorouracil at a dose of 2400 mg/m² via 46-hour infusion.Dosing may follow the above regimen or local institutional standards. Intravenous leucovorin at a dose of 400 mg/m².Dosing may follow the above regimen or local institutional standards. Intravenous irinotecan at a dose of 150 mg/m².Dosing may follow the above regimen or local institutional standards. Intravenous oxaliplatin at a dose of 85 mg/m².Dosing may follow the above regimen or local institutional standards. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Periodo de tiempo: First 28 days (21 days for AG （3-week cycle）)
|
The incidence of DLT events |
First 28 days (21 days for AG （3-week cycle）)
|
|
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
Periodo de tiempo: From the first dose until 30 days after the last dose, assessed up to 24 months
|
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0 |
From the first dose until 30 days after the last dose, assessed up to 24 months
|
|
Phase II:Objective Response Rate (ORR)
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Assessed by investigators according to RECIST 1.1 |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
Phase Ib: Number of participants with abnormality in hematology laboratory parameters
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality in hematology laboratory parameters，Hematology assessments will include hemoglobin, white blood cell count, differential white blood cell counts and platelet count |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in clinical chemistry laboratory assessments
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality in clinical chemistry laboratory assessments， assessments will include serum chemistry (such as sodium, potassium, urea, creatinine) and liver function parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin. |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in body temperature
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality in body temperature(°C), throughout the study. |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in blood pressure
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality in blood pressure, including systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in Physical Examination Findings
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality in Physical Examination Findings |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in PR interval
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality in electrocardiogram (ECG) parameters, including PR interval |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in corrected QT interval using Frederica's formula (QTcF)
Periodo de tiempo: up to 24 months
|
Number of participants with abnormality incorrected QT interval using Frederica's formula (QTcF) |
up to 24 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase II: Incidence and Severity of AE and SAE
Periodo de tiempo: From the first dose until 30 days after the last dose, assessed up to 24 months
|
Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0 |
From the first dose until 30 days after the last dose, assessed up to 24 months
|
|
DCR
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Disease Control Rate (DCR) |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
DoR
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Duration of Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
TTR
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Time To Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
PFS
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
OS
Periodo de tiempo: From the first dose until date of death from any cause, assessed up to 24 months
|
Overall Survival |
From the first dose until date of death from any cause, assessed up to 24 months
|
|
Time to peak plasma concentration（Tmax） of GFH276
Periodo de tiempo: up to 6 months
|
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Tmax were evaluated. |
up to 6 months
|
|
Maximum plasma concentration of GFH276
Periodo de tiempo: up to 6 months
|
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Cmax were evaluated. |
up to 6 months
|
|
Area Under the Curve from time zero to 24 hours of GFH276
Periodo de tiempo: up to 6 months
|
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including AUC0-24 were evaluated. |
up to 6 months
|
Colaboradores e Investigadores
Patrocinador
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
Palabras clave
Términos MeSH relevantes adicionales
- Aminoácidos, péptidos y proteínas
- Proteínas
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Campeptecina
- Alcaloides
- Enzimas y coenzimas
- Anticuerpos, monoclonales, humanizados
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Complejos de coordinación
- Desoxicitidina
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Economía y organizaciones de la atención médica
- Formiltetrahidrofolatos
- Tetrahidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Uracílico
- Pirimidinonas
- Coenzimas
- Ciencias económicas
- Oxaliplatino
- Irinotecán
- Cetuximab
- Gemcitabina
- Fluorouracilo
- Leucovorina
- Impuestos
Otros números de identificación del estudio
- GFH276X0201
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.
producto fabricado y exportado desde los 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. .