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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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).
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: Revolution Medicines Study Director
- Telefonní číslo: 1-844-2-REVMED
- E-mail: medinfo@revmed.com
Studijní místa
-
-
Arizona
-
Phoenix, Arizona, Spojené státy, 85054
- Nábor
- Mayo Clinic Arizona
-
Kontakt:
- Tanios S. Bekaii-Saab
- Telefonní číslo: 855-776-0015
-
Scottsdale, Arizona, Spojené státy, 85258
- Nábor
- HonorHealth Research Institute
-
Kontakt:
- Amy Malensek
- Telefonní číslo: 480-323-1350
- E-mail: amalensek@honorhealth.com
-
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Florida
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Jacksonville, Florida, Spojené státy, 32224
- Nábor
- Mayo Clinic Florida
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Kontakt:
- Hani M. Babiker
- Telefonní číslo: 855-776-0015
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Tampa, Florida, Spojené státy, 33612
- Nábor
- Moffitt Cancer Center
-
Kontakt:
- Cheyenne Schneider
- Telefonní číslo: 813-745-5166
- E-mail: Cheyenne.Schneider@moffitt.org
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Minnesota
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Rochester, Minnesota, Spojené státy, 55905
- Nábor
- Mayo Clinic Rochester
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Kontakt:
- Ben George
- Telefonní číslo: 855-776-0015
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Rhode Island
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Providence, Rhode Island, Spojené státy, 02903
- Nábor
- Rhode Island Hospital
-
Kontakt:
- Andrew Schumacher
- Telefonní číslo: 401-444-3234
- E-mail: aschumacher@brownhealth.org
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Arm A: daraxonrasib + zoldonrasib
combination of study drugs |
oral tablets oral tablets |
|
Experimentální: Arm B: gemcitabine and nab-paclitaxel
chemotherapy |
IV infusion intravenous (IV) infusion |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall survival (OS)
Časové okno: 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)
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Incidence of adverse events (AEs)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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)
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Onemocnění endokrinního systému
- Novotvary podle místa
- Novotvary
- Novotvary trávicího systému
- Nemoci trávicího systému
- Novotvary endokrinních žláz
- Onemocnění slinivky břišní
- Novotvary pankreatu
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Deoxycytidin
- Cytidin
- Pyrimidinové nukleosidy
- Pyrimidiny
- Gemcitabin
- 130 nm albumin vázaný na paclitaxel
Další identifikační čísla studie
- RMC-9805-309
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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