PABLIXIMAB as Neoadjuvant Therapy for Head and Neck Squamous-cell Carcinoma

Официальное название

A Single-arm, Prospective, Phase II Study of PABLIXIMAB Combined With TP Chemotherapy as Neoadjuvant Therapy for Locally Advanced Head and Neck Squamous-cell Carcinoma

Обзор

The goal of this clinical trial is to learn about the efficacy and safety of pablizumab combined with neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma. The main question it aims to answer is: Pathological complete remission (PCR) rate of tumor after neoadjuvant immunotherapy. Participants will be asked to perform CT and MRI of head and neck, ultrasonography of cervical lymph nodes and necessary laboratory examinations Before and after neoadjuvant therapy. And will be following-up for at least 1 year.

Подробное описание

The secondary questions it aims to answer are:

Objective response rate (ORR) after neoadjuvant therapy

* R0 resection rate * major pathological remission (MPR) rate * organ preservation rate * event-free survival (EFS) * local recurrence-free survival (LRFS) * distant metastasis-free survival (DMFS) * quality of life score (QoL) * overall survival (OS) * incidence of adverse events (including neoadjuvant stage AEs and full course AEs) The exploratory question it aims to answer is: clearance of peripheral blood ctDNA.

Первичные конечные точки

• Pathological complete remission (pCR) rate of tumor after neoadjuvant immunotherapy. [Срок оценки: About 50 days after the start of neoadjuvant immunotherapy.]

Вторичные конечные точки (5)

• ORR(objective response rate) [Срок оценки: At least 1 year.]
• R0 resection rate [Срок оценки: At least 1 year.]
• MPR（major pathological response） [Срок оценки: At least 1 year.]
• Overall survival rate [Срок оценки: At least 1 year.]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Срок оценки: At least 1 year.]

Критерии участия

Критерии включения

• age 18-80 years old, including 18 years old and 80 years old;
• MRI diagnosis of resectable stage III-IVA oropharynx, larynx and hypopharynx squamous-cell carcinoma confirmed by histopathology or cytology;
• ECOG PS score 0-1;
• the expression of PD-L1 was detected by immunohistochemistry (TPS and CPS score)
• having at least one measurable lesion according to RECIST version 1.1;
• expected survival time ≥6 months;
• The neutrophil count was ≥1.5 × 10\^9/L, the platelet count was ≥100 × 10\^9/L, the hemoglobin count was ≥90 g/L
• renal function was normal: serum creatinine ≤1.5×ULN;
• the liver function was basically normal: serum total bilirubin ≤1.5 × ULN, serum aspartate transaminase (AST)≤2.5×ULN, serum Alanine transaminase (ALT)≤2.5 ×ULN;
• female patients had to be negative for a urine pregnancy test before the start of the study (not applicable to patients with bilateral oophorectomy and/or hysterectomy or postmenopausal patients) ;
• Sign the written informed consent.

Критерии исключения

• patients were treated with anti-tumor drugs including but not limited to PD-1 inhibitor, CTLA-4 antibody, EGFR monoclonal antibody, EGFR-tki, and anti-angiogenesis drugs;
• History of autoimmune diseases including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, Rheumatoid Arthritis, inflammatory bowel disease, Antiphospholipid syndrome vascular thrombosis, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
• participated in other intervention clinical trials within 30 days before screening;
• history of other malignancies (except cured skin basal-cell carcinoma) ;
• the presence of serious and poorly controlled co-morbidities (e.g. heart failure, diabetes, hypertension, liver failure, kidney failure, thyroid disease, mental illness, etc.) ;
• Known to be infected with HIV or active hepatitis or tuberculosis;
• major surgery or planned surgery within 30 days before the first dose of the trial drug;
• Persons who are allergic to the use of drugs or their components in the programme;
• pregnancy (confirmed by blood or urine HCG testing) or lactation in women, or in subjects of reproductive age who were unwilling or unable to use effective contraception (for both male and female subjects) until at least 6 months after the last trial treatment;
• it is not suitable for the researcher to participate in this study;
• Unwilling to participate in the study or unable to sign the informed consent.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020 Nov 26;6(1):92. doi: 10.1038/s41572-020-00224-3. PMID 33243986
• Keam B, Machiels JP, Kim HR, Licitra L, Golusinski W, Gregoire V, Lee YG, Belka C, Guo Y, Rajappa SJ, Tahara M, Azrif M, Ang MK, Yang MH, Wang CH, Ng QS, Wan Zamaniah WI, Kiyota N, Babu S, Yang K, Curigliano G, Peters S, Kim TW, Yoshino T, Pentheroudakis G. Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous PMID 34844180
• Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D, Birkeland AC, Brizel DM, Busse PM, Cmelak AJ, Colevas AD, Eisele DW, Galloway T, Geiger JL, Haddad RI, Hicks WL, Hitchcock YJ, Jimeno A, Leizman D, Mell LK, Mittal BB, Pinto HA, Rocco JW, Rodriguez CP, Savvides PS, Schwartz D, Shah JP, Sher D, St John M, Weber RS, Weinstein G, Worden F, Yang Bruce J, Yom SS, Zhen W, Burns JL, Dar PMID 35276673
• Bhatia A, Burtness B. Treating Head and Neck Cancer in the Age of Immunotherapy: A 2023 Update. Drugs. 2023 Feb;83(3):217-248. doi: 10.1007/s40265-023-01835-2. Epub 2023 Jan 16. PMID 36645621
• Veigas F, Mahmoud YD, Merlo J, Rinflerch A, Rabinovich GA, Girotti MR. Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma. Cancers (Basel). 2021 Mar 1;13(5):1018. doi: 10.3390/cancers13051018. PMID 33804419
• Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph R, Weber JS, Dronca R, Mitchell TC, Patnaik A, Zarour HM, Joshua AM, Zhao Q, Jensen E, Ahsan S, Ibrahim N, Ribas A. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019 Apr 1;30(4):582-588. doi: 10.1093/annonc/mdz011. PMID 30715153
• Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metas PMID 31679945

Идентификаторы

NCT: NCT06125223 · KY20232325

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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