Neoadjuvant Merkel Cell Carcinoma Therapy (Tx) With the PD-1 Inhibitor Cemiplimab

Официальное название

Neoadjuvant Merkel Cell Carcinoma Therapy (Tx) With the PD-1 Inhibitor Cemiplimab - A Randomized, Double-blind, Placebo-controlled, Non-comparative Phase II Study

Обзор

The study is a randomized, double blind, placebo-controlled, non-comparative phase II trial that investigates the efficacy of neoadjuvant anti-PD-1 antibody Cemiplimab treatment in patients with clinical stage I or II Merkel cell carcinoma who have have undergone primary tumour excision and are pending sentinel lymph node biopsy.

Вмешательства

• Препарат Cemiplimab 350 mg i.v. on day 1 of every 21 days cycle for 2 cycles
  Patients will receive Cemiplimab 350 mg i.v. on day 1 of every 21 days cycle for 2 cycles
• Препарат Placebo NaCl 0.9% solution i.v. on day 1 of every 21 days cycle for 2 cycles.
  Patients will receive NaCl 0.9% solution i.v. on day 1 of every 21 days cycle for 2 cycles.

Первичные конечные точки

• Nodal micrometastases-free rate [Срок оценки: up to 36 months]

Вторичные конечные точки (6)

• Recurrence-free survival [Срок оценки: up to 66 months]
• Overall survival [Срок оценки: up to 66 months]
• Disease specific survival [Срок оценки: up to 66 months]
• Quality of life using FCRI-SF questionnaire [Срок оценки: up to 66 months]
• Safety (AEs and SAEs) [Срок оценки: up to 66 months]
• Quality of life using the mFACT-M questionnaire [Срок оценки: up to 66 months]

Критерии участия

Критерии включения

• Patient has signed informed written consent.
• Patients is 18 years and older at time of signing of written informed consent
• Patient has diagnosis of Merkel cell carcinoma in clinical stage II, or in stage I with minimum diameter of 1 cm, with primary tumor already removed and a planned sentinel lymph nodes biopsy still pending.
• Patient has ECOG performance status 0-2.
• Patients has adequate laboratory parameters particularly for the blood count, renal and liver function parameters.

• Absolute number of neutrophils ≥ 1.5 x 109/L
• Platelets ≥ 75 x 109/L
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with Gilbert´s Disease and total bilirubin up to 3x ULN may be eligible after approval from trial's medical expert)
• AST (SGOT) and ALT (SGPT) ≤ 3x ULN
• AP ≤ 2.5x ULN
• Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL/min
• Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of Cemiplimab. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.
• Patient must be willing to allow translational work-up of tissue samples (PT, sentinel lymph node biopsy).

Критерии исключения

• Patient has prior sentinel lymph node removal for the current MCC.
• Patients received prior treatment with immunotherapy (such as PD-1/PD-L1 or CTL4) or any other systemic anti-tumor (MCC) therapy (incl. investigational therapies)
• Patient has active or a history of hematological neoplasms including chronic lymphocytic leukemia (CLL), irrespective if these require treatment or not.
• Patient had prior organ transplantation including allogenic stem-cell transplantation.
• Patient receives immunosuppressive concomitant medication, EXCEPT for the following:

i. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection).

ii. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent.

iii. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

• Patient has known hypersensitivity to any component of the Cemiplimab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
• Patient has active autoimmune or inflammatory disorders.
• Patient has history of interstitial lung disease.
• Patient has active infection requiring systemic therapy.
• Patient has Active infection requiring systemic therapy, including uncontrolled HIV, HBV and HCV infection or diagnosis of immunodeficiency.

NOTE: Patients are eligible if:

• Patients have controlled HIV infection with CD4 counts is > 350 cells/μL and viral load is undetectable \[HIV RNA PCR\]. Patients with controlled HIV infection must be monitored per local standards during the trial.
• Patients positive for HBV surface antigen have controlled HBV infection receiving anti-viral therapy and with undetectable serum viral load \[HBV DNA PCR\]. Patients with controlled infection must undergo periodic monitoring of HBV DNA and p must remain on anti-viral therapy for at least 6 months after last dose of Cemiplimab.
• Patients positive for HCV antibody have controlled HCV infection with undetectable viral load \[HCV RNA PCR\].
• Patent received vaccination with any live vaccine (e.g., intranasal flu vaccine) within 4 weeks before the first dose of Cemiplimab or planned vaccination with live vaccine during the trial
• Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum β-HCG pregnancy test result within 7 days prior to initiation of study treatment.
• Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.
• Patient has known substance abuse or other psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Patient is legally incapacitated or has limited legal capacity

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Германия · 14 центров

• Nationales Centrum für Tumorerkrankungen — Heidelberg
• Universitätsklinikum Mannheim — Mannheim
• Universitätsklinikum Tübingen — Tübingen
• Universitätsklinikum Regensburg — Regensburg
• Universitätsklinikum Würzburg — Würzburg
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Universitätsklinikum Frankfurt — Frankfurt am Main
• Klinikum Bielefeld — Bielefeld
• … и ещё 6 центров

Идентификаторы

NCT: NCT07387198 · NeoMatryx

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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