Trial to Evaluate irAEs With Different Standard of Care Dosing Strategies of Standard of Care Immunotherapies

Официальное название

A Late Phase Randomized Open-Label Multi Cohort Trial to Evaluate irAEs With Different Standard of Care Dosing Strategies of Standard of Care Immunotherapies

Обзор

Phase 3/4 open label, randomized two cohort study (2 arms in each cohort). It is hypothesized that for people with a histologically or cytologically confirmed diagnosis of malignancy, the higher dose immunotherapy (every 6 weeks Pembrolizumab 400mg dose and every 4 weeks Nivolumab 480mg dose) has more immune-related adverse events irAEs compared to lower dose (every 3 weeks Pembrolizumab 200mg dose and every 2 weeks Nivolumab 240mg dose).

Вмешательства

• Препарат Nivolumab
  Immunotherapy
• Препарат Pembrolizumab
  Immunotherapy

Первичные конечные точки

• Proportions of grade ≥3 immune related adverse events (irAEs) between the two arms in each cohort [Срок оценки: 12 weeks]

Вторичные конечные точки (7)

• All grades of immune related adverse events (irAEs) [Срок оценки: Start of treatment to EOT. Approximate time frame 6-12 months.]
• Time to resolution of immune related adverse events (irAEs) [Срок оценки: Start of treatment to end of follow up. Approximate Time Frame: 2-3 Years]
• Time of treatment discontinuation due to immune related adverse events (irAEs) [Срок оценки: Start of treatment to discontinuation Approximate Time Frame: 12 Months]
• Overall Response Rate (ORR) [Срок оценки: Approximate time frame: 12 weeks]
• Disease-Free Survival (DFS) [Срок оценки: 6 months, 1 year, and 2 yearsApproximate time frame 3 years.]
• Progression-Free Survival (PFS) [Срок оценки: 6 months, 1 year, and 2 yearsApproximate time frame 3 years.]
• Overall Survival (OS) [Срок оценки: Approximate time frame: 2 years]

Критерии участия

Критерии включения

• Ability of participant to understand this study, and participant willingness to sign a written informed consent.
• Males and females age ≥ 18 years
• ECOG Performance Status (PS) 0 - 2 (Appendix A.)
• Females of childbearing potential must have a negative urine pregnancy test 72 hours prior to initiating treatment.
• Histologically or cytologically confirmed diagnosis of solid tumor malignancy
• Eligible to receive pembrolizumab or nivolumab based therapy
• Any disease setting (neoadjuvant, adjuvant, unresectable, metastatic) or any line of therapy is allowed. NOTE: Standard of care combination agents(chemotherapy, targeted therapy, biologics) are allowed because irAEs are the primary objective
• Adequate organ function, defined as follows:

Leukocytes (White Blood Cell \[WBC\]) >1.0 K/UL Absolute Neutrophil Count >1.0 K/UL Platelets > 50 K/UL Hemoglobin ≥ 7 g/dL Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation Total bilirubin ≤ 1.5 x ULN Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN

Критерии исключения

• Simultaneously enrolled in any therapeutic clinical trial
• Concurrent or planned use of other immunotherapies or radiation
• Has not recovered from irAEs due to prior immunotherapy treatment (>=grade 2 is considered not recovered). Conditions that meet grade 2 criteria but are considered clinically stable at the discretion of the investigator will be allowed.
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Currently pregnant or breastfeeding
• Has a known allergic reaction to any excipient contained in the study drug formulation
• Active Grade 3 (per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 ) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.

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 · 1 центр

• The University of Kansas Cancer Center — Westwood

Публикации

• Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 M PMID 28271869
• Persigehl T, Lennartz S, Schwartz LH. iRECIST: how to do it. Cancer Imaging. 2020 Jan 3;20(1):2. doi: 10.1186/s40644-019-0281-x. PMID 31900236
• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. PMID 19097774
• U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Oncology Center of Excellence (OCE). Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices Guidance for Industry - Draft Guidance. Dece
• The University of Kansas Cancer Center Clinical Trials Office Policy - Executive Resourcing Committee Submission Requirements. Version dated 08-03-2022. Cited 09-20-2024. Available from: https://kumed.sharepoint.com/sites/mykumc/cto/Documents/CTO%20Policy_ERC%20Submission.pdf#search=executive%20resource Accessed 09-20-2024
• The University of Kansas Cancer Center General Administration Guidance Document - Use of Investigator Initiated Steering Committee. Version dated 07-31-2023. Cited 09-20-2024. Available from: https://kumed.sharepoint.com/sites/mykumc/cto-training/Documents/Guidance_Use%20of%20Investigator%20Initiated%20Steering%20Committee.pdf#search=steering%20committee%20guidance%20document Accessed 09-20-2024
• European Medicines Agency. ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. June 1995. https://www.ema.europa.eu/en/ich-e2a-clinical-safety-data-management-definitions-standards-expedited-reporting-scientific-guideline . Cited 12-06-2024
• National Institute of Health/National Cancer Institute - Cancer Therapy Evaluation Program (CTEP). Common Terminology Criteria for Adverse Events (CTCAE). Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_60 Accessed 07-05-2023.

Идентификаторы

NCT: NCT07174453 · STUDY00161901

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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