A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected PDAC

Официальное название

A Phase II, Open-Label, Multicenter, Randomized Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Patients With Resected Pancreatic Ductal Adenocarcinoma

Обзор

The purpose of this study is to evaluate the efficacy and safety of adjuvant autogene cevumeran plus atezolizumab and modified leucovorin, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (mFOLFIRINOX) versus mFOLFIRINOX alone in participants with resected pancreatic ductal adenocarcinoma (PDAC) who have not received prior systemic anti-cancer treatment for PDAC and have no evidence of disease after surgery.

Вмешательства

• Препарат Autogene cevumeran
  Autogene cevumeran will be administered intravenously (IV) at a recommended dose at specified timepoints.
• Препарат Atezolizumab
  Atezolizumab will be administered IV at a dose of 1680 milligrams (mg) at specified timepoints.
• Препарат mFOLFIRINOX
  mFOLFIRINOX (oxaliplatin, leucovorin, irinotecan, 5-FU) will be administered IV at specified timepoints.

Первичные конечные точки

• Disease Free Survival (DFS) [Срок оценки: From randomization to first recurrence of PDAC or first occurrence of new cancer, as determined by the investigator, or death from any cause (whichever occurs first), up to approximately 6 years]

Вторичные конечные точки (4)

• DFS Rates at 12, 24, and 36 Months [Срок оценки: Months 12, 24, 36]
• Overall Survival (OS) [Срок оценки: From randomization to death from any cause (up to approximately 6 years)]
• OS Rates at 3 and 5 Years [Срок оценки: Years 3 and 5]
• Percentage of Participants With Adverse Events (AEs) [Срок оценки: Up to approximately 6 years]

Критерии участия

Критерии включения

• Histologically confirmed diagnosis of PDAC
• Pancreatic cancer tumor, lymph node, metastasis (TNM) pathological staging values of T1-T3, N0-N2, and M0 per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual
• Macroscopically complete (R0 or R1) resection of PDAC
• Unequivocal absence of disease after surgery as assessed by the investigator within 28 days prior to treatment initiation
• CA19-9 level measured within 14 days prior to initiation of study treatment
• Interval of between 6 and 12 weeks since resection of PDAC
• Full recovery from surgery and ability to receive atezolizumab, autogene cevumeran, and mFOLFIRINOX in the investigator's judgment
• Adequate hematologic and end-organ function
• Female participants of childbearing potential must be willing to avoid pregnancy during the treatment period and for 28 days after the final dose of autogene cevumeran, for 9 months after the last dose of chemotherapy, and for 5 months after the final dose of atezolizumab. They must refrain from donating eggs for 9 months after the last dose of chemotherapy.
• Male participants with a female partner of childbearing potential or pregnant female partner must remain abstinent or use specified contraceptive methods during the treatment period and for 28 days after the final dose of autogene cevumeran and for 6 months after the last dose of chemotherapy. Men must refrain from donating sperm during this same period.

Критерии исключения

• Prior adjuvant, neoadjuvant, or induction treatment for pancreatic cancer
• Plan for further adjuvant anti-cancer therapy for PDAC (e.g., radiotherapy and/or chemotherapy), not mandated per protocol, to be initiated after completion of mFOLFIRINOX treatment
• Absence of spleen; distal pancreatectomy with splenectomy is exclusionary
• Preexisting Grade >/=2 neuropathy
• Known complete dihydropyrimidine dehydrogenase (DPD) deficiency including homozygous or compound heterozygous mutations of DPYD genetic locus associated with DPD deficiency
• Disorders of the colon or rectum, or postoperative complication leading to Grade >/=2 diarrhea
• Pregnancy or breastfeeding
• Active or history of autoimmune disease or immune deficiency
• Treatment with brivudine, sorivudine, or their chemically-related analogues, which are inhibitors of DPD, within 4 weeks prior to initiation of study treatment
• Current or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) and/or uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 32 центра

• USC Norris Comprehensive Cancer Center — Los Angeles
• USC Norris Cancer Center — Newport Beach
• University of California, San Francisco (UCSF) — San Francisco
• University of California Los Angeles — Santa Monica
• St. Francis Hospital and Medical Center — Hartford
• Smilow Cancer Center — New Haven
• Yale Cancer Center — New Haven
• Smilow Cancer Hospital Care Center at Trumbull — Trumbull
• … и ещё 24 центра

Германия · 13 центров

• Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) — Berlin
• Katholisches Klinikum Bochum gGmbH;St. Josef-Hospital — Bochum
• Universitaetsklinikum Koeln — Cologne
• Universitätsklinikum Carl Gustav Carus Dresden — Dresden
• Universitätsklinikum Essen — Essen
• Krankenhaus Nordwest GmbH — Frankfurt
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Universitaetsklinikum Heidelberg — Heidelberg
• … и ещё 5 центров

Испания · 10 центров

• Institut Catala d?Oncologia Hospital Germans Trias i Pujol — Badalona
• Hospital Regional Universitario de Malaga — Málaga
• Clinica Universitaria de Navarra (CUN) — Pamplona/iruña
• Hospital Universitario Central de Asturias — Oviedo
• Hospital Universitario Vall d Hebron — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Clinica Universitaria de Navarra de Madrid;Servicio de Hepatologia — Madrid
• Hospital Universitario Ramón y Cajal — Madrid
• … и ещё 2 центра

Великобритания · 8 центров

Список центров уточняется — проверьте первичный протокол.

South Korea · 7 центров

• National Cancer Center (NCC) Hospital - Center for Liver and Pancreatobiliary Cancer — Goyang-si
• CHA Bundang Medical Center — Gyeonggi-do
• The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital) — Seocho
• Seoul National University Bundang Hospital — Seongnam-si
• Samsung Medical Center — Seoul
• Severance Hospital - Yonsei Cancer Center — Seoul
• University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center ( — Songpa-gu

Бельгия · 5 центров

• Antwerp University Hospital — Edegem
• ULB Hôpital Erasme — Brussels
• AZ Maria Middelares — Ghent
• Universitair Ziekenhuis Gent — Ghent
• UZ Leuven — Leuven

Франция · 5 центров

• Centre Hospitalier Régional Universitaire de Lille — Lille
• Centre Leon Berard — Lyon
• Institut Paoli Calmettes — Marseille
• Institut de Cancérologie de Lorraine — Vandœuvre-lès-Nancy
• Gustave Roussy — Villejuif

Канада · 4 центра

• St Michael Hospital — Toronto
• Princess Margaret Cancer Center — Toronto
• Centre Hospitalier de l'Universite de Montreal - Notre - Dame Hos pital — Montreal
• Jewish General Hospital — Montreal

Нидерланды · 3 центра

• Amsterdam UMC Location VUMC — Amsterdam
• UMC Radboud Nijmegen — Nijmegen
• Erasmus MC — Rotterdam

Швеция · 2 центра

• Sahlgrenska Universitetssjukhuset — Gothenburg
• … и ещё 1 центр

Идентификаторы

NCT: NCT05968326 · GO44479 · 2022-502404-73-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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