Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma (RASolute 309)
A Phase 3, Randomized, Open-Label Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Patients With Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma
The purpose of this study is to evaluate the efficacy of combination therapy with two investigational RAS(ON) inhibitors (daraxonrasib and zoldonrasib) compared to chemotherapy.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib plus zoldonrasib will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic KRAS G12D-mutated pancreatic adenocarcinoma.
Patients will be randomized to one of two arms: daraxonrasib + zoldonrasib (Arm A) or gemcitabine and nab-paclitaxel (Arm B).
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
- Nome: Revolution Medicines Study Director
- Número de telefone: 1-844-2-REVMED
- E-mail: medinfo@revmed.com
Locais de estudo
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Arizona
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Phoenix, Arizona, Estados Unidos, 85054
- Recrutamento
- Mayo Clinic Arizona
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Contato:
- Tanios S. Bekaii-Saab
- Número de telefone: 855-776-0015
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Scottsdale, Arizona, Estados Unidos, 85258
- Recrutamento
- HonorHealth Research Institute
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Contato:
- Amy Malensek
- Número de telefone: 480-323-1350
- E-mail: amalensek@honorhealth.com
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Recrutamento
- Mayo Clinic Florida
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Contato:
- Hani M. Babiker
- Número de telefone: 855-776-0015
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Tampa, Florida, Estados Unidos, 33612
- Recrutamento
- Moffitt Cancer Center
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Contato:
- Cheyenne Schneider
- Número de telefone: 813-745-5166
- E-mail: Cheyenne.Schneider@moffitt.org
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Recrutamento
- Mayo Clinic Rochester
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Contato:
- Ben George
- Número de telefone: 855-776-0015
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Rhode Island
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Providence, Rhode Island, Estados Unidos, 02903
- Recrutamento
- Rhode Island Hospital
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Contato:
- Andrew Schumacher
- Número de telefone: 401-444-3234
- E-mail: aschumacher@brownhealth.org
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- At least 18 years old and has provided informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically or cytologically confirmed pancreatic adenocarcinoma, including adenosquamous carcinoma, not previously treated in the locally advanced unresectable or metastatic setting.
- No prior treatment in the locally advanced unresectable or metastatic setting
- Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
- Documented KRAS G12D mutation status.
- Measurable disease per RECIST v1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation).
Exclusion Criteria:
- Mutation status with known driver mutations for which there are approved targeted therapies.
- Acinar cell carcinoma, pancreatic neuroendocrine tumors, tumors involving islet cells or islet cell neoplasms, and other non-adenocarcinoma pancreatic malignancies.
- Tumors determined to originate from non-pancreatic primary sites.
- Prior treatment with MAPK-pathway targeted therapy or administration of RAS-targeted vaccine in the metastatic setting.
- Active or known history of untreated central nervous system metastatic or leptomeningeal disease.
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery within 28 days prior to randomization.
- Patient is unable or unwilling to comply with protocol-required study visits or procedures.
- Additional inclusion & exclusion criteria may apply.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Arm A: daraxonrasib + zoldonrasib
combination of study drugs |
oral tablets oral tablets |
|
Experimental: Arm B: gemcitabine and nab-paclitaxel
chemotherapy |
IV infusion intravenous (IV) infusion |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Overall survival (OS)
Prazo: Up to approximately 4 years
|
OS is defined as the time from randomization until death from any cause. |
Up to approximately 4 years
|
|
Progression free survival (PFS)
Prazo: Up to approximately 4 years
|
PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by Investigator. |
Up to approximately 4 years
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of adverse events (AEs)
Prazo: Up to approximately 4 years
|
Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 |
Up to approximately 4 years
|
|
Changes in clinical laboratory test values
Prazo: Up to approximately 4 years
|
Number of patients with changes from baseline in clinical laboratory test values |
Up to approximately 4 years
|
|
Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) pain scale
Prazo: Up to approximately 4 years
|
EORTC QLQ-PAN26 consists of 26 questions relating to disease symptoms, treatment side effects and emotional issues specific to pancreatic cancer. The pancreatic pain subscale assesses abdominal pain, back pain, and pain while lying down. Change in score from baseline in the pain subscale will be assessed with higher scores on the pain subscale indicating more severe pain and worsening function. |
Up to approximately 4 years
|
|
Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status score
Prazo: Up to approximately 4 years
|
EORTC QLQ-C30 consists of 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties), and an overall scale for global health status. It uses a mix of 4-point scales and 7-point scales. Change from baseline in EORTC QLQ-C30 global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden. |
Up to approximately 4 years
|
|
PFS by blinded independent central review (BICR)
Prazo: Up to approximately 4 years
|
PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed per RECIST v1.1 by BICR |
Up to approximately 4 years
|
|
Objective response rate (ORR)
Prazo: Up to approximately 4 years
|
Objective response is defined as partial response (PR) or complete response (CR) per RECIST v1.1, as assessed by the Investigator. |
Up to approximately 4 years
|
|
Duration of response (DOR)
Prazo: Up to approximately 4 years
|
DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by the investigator. |
Up to approximately 4 years
|
|
Changes in vital signs
Prazo: Up to approximately 4 years
|
Number of patients with changes from baseline in vital signs |
Up to approximately 4 years
|
|
Concentration of daraxonrasib and zoldonrasib in Arm A
Prazo: Up to Cycle 5 Day 1 (each cycle is 28 days)
|
Pre-dose trough and post-dose blood concentrations of daraxonrasib and zoldonrasib at selected visits. |
Up to Cycle 5 Day 1 (each cycle is 28 days)
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do Sistema Endócrino
- Neoplasias por local
- Neoplasias
- Neoplasias do Aparelho Digestivo
- Doenças do aparelho digestivo
- Neoplasias das Glândulas Endócrinas
- Doenças pancreáticas
- Neoplasias Pancreáticas
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Desoxicitidina
- Citidina
- Nucleosídeos de pirimidina
- Pirimidinas
- Gemcitabina
- Paclitaxel com 130 nm de albumina
Outros números de identificação do estudo
- RMC-9805-309
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