Towards Cure Via Only Ultra-short ICB in CSCC

Официальное название

Towards Organ Preservation and Cure Via Immunotherapy in Cutaneous Squamous Cell Carcinoma Patients, Normally Undergoing Morbid Curative Surgery and Radiotherapy. The MATISSE 2 Trial, an Investigator-initiated Multicentre Phase 2 Trial

Обзор

The goal of this clinical trial is to determine whether cutaneous squamous cell carcinoma patients can be cured using only immunotherapy, without surgery or radiotherapy.

Подробное описание

This is an investigator-initiated phase 2 clinical trial consisting of 41 patients with stage I-IVa CSCC and an indication for morbid/extensive curative surgery. All patients will receive two courses of nivolumab 3 mg/kg in week 0 and week 2, and one course of ipilimumab 1 mg/kg in week 0. In week 5 response to immunotherapy will be evaluated using clinical examination, \[18F\]FDG-PET/CT imaging, regional lymph node ultrasound with FNAC (if applicable) and a multicentre multidisciplinary meeting. Non-responders will receive standard of care surgery (w/wo radiotherapy). Responders will enter a wait-and-monitor follow-up schedule in which response will be monitored every 3 months for a total of 2 years. If a patient is no longer responding to immunotherapy during follow-up they will receive standard of care surgery (w/wo radiotherapy).

Вмешательства

• Препарат Nivolumab
  3 mg/kg
• Препарат Ipilumimab
  1 mg/kg

Первичные конечные точки

• Rate of clinical complete remission after only immunotherapy [Срок оценки: From the start of immunotherapy until 24 months of follow-up]

Вторичные конечные точки (12)

• Rate of clinical complete remission after only immunotherapy [Срок оценки: From the start of immunotherapy until 12 and 18 months of follow-up.]
• Immune-related adverse events [Срок оценки: From the start of immunotherapy until 100 days after the last course of immunotherapy.]
• Health-related quality of life (EORTC QLQ-C30) [Срок оценки: From the start of immunotherapy until 24 months of follow-up.]
• Health-related quality of life (EORTC QLQ-H&N35) [Срок оценки: From the start of immunotherapy until 24 months of follow-up.]
• Health-related quality of life (EQ5D) [Срок оценки: From the start of immunotherapy until 24 months of follow-up.]
• Health-related quality of life (CWS) [Срок оценки: From the start of immunotherapy until 24 months of follow-up.]
• Health-related quality of life (IT) [Срок оценки: From the start of immunotherapy until 24 months of follow-up.]
• Health-related quality of life (sexuality questionnaire) [Срок оценки: From the start of immunotherapy until 24 months of follow-up.]
• Treatment duration [Срок оценки: From the start of immunotherapy until the end of treatment (average 6 weeks)]
• Treatment stops [Срок оценки: From the start of immunotherapy until the end of treatment (average 6 weeks)]
• Disease-specific survival [Срок оценки: From the start of immunotherapy until 2 years follow-up.]
• Recurrence-free survival [Срок оценки: From the start of immunotherapy until 2 years follow-up.]

Критерии участия

Критерии включения

• 18 years of age or older
• UV-related stage I to IVa CSCC with an indication for extensive or disfiguring surgery
• Stage III-IVa CSCC (T3-4N0-3M0 or T0N1-3M0) or multi-focal stage I-II CSCC
• Primary tumour site: vermillion border lip (C00.0, C00.1, C00.2), skin of lip NOS (C44.0), external ear (C44.2), skin face unspecified (ao: external lip and vestibulum nasi) (C44.3), skin scalp and neck (C44.4), overlapping lesion of skin (C44.8), primary site eyelid (C44.1), other body sites: CSCC outside head and neck area, but not vulva, anus or penis.
• World Health Organisation (WHO) performance status of 0-2
• Indication for SOC surgery with curative intent ± RT
• Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.5x109 /L, Platelets ≥100 x109 /L, Haemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x upper limit of normal (ULN), AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN (except patients with Gilbert Syndrome, who are eligible when total bilirubin < 3.0 mg/dL).
• Women of child-bearing potential (WOCBP) must use appropriate method(s) of contraception. They should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required time for nivolumab to undergo five x T1/2) after the last dose of the IMP.
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of ICB.
• Patients willing and able to understand the Dutch study information and protocol requirements and comply with the treatment/intervention schedule, scheduled visits, and other requirements of the study.

Критерии исключения

• Distantly metastasized (stadium IVb) CSCC
• SCC localized in a mucosal surface (i.e. anus, vulva, penis or mucosal portion of lip)
• Patients for whom standard of care treatment consists of definitive (brachy)radiotherapy
• Primary or recurrent CSCC appearing in an area that has been previously irradiated
• Prior systemic therapy or immunotherapy.
• Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)
• Subjects with any active autoimmune disease or a documented history of autoimmune disease, except: subjects with vitiligo, resolved childhood asthma/atopy, residual hypothyroidism due to an autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, any condition not expected to recur in the absence of an external trigger.
• Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity or AEs
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids (up to 5 mg of prednisone per day is allowed)
• Patients who are pregnant or breastfeeding
• History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody
• Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 5 центров

• Maastricht UMC — Maastricht
• Netherlands Cancer Institute - Antoni van Leeuwenhoek — Amsterdam
• Amsterdam UMC — Amsterdam
• Erasmus MC — Rotterdam
• UMC Utrecht — Utrecht

Идентификаторы

NCT: NCT06823479 · M24MAT · 2024-516152-17-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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