Clinical trial NCT06823479: Towards Cure Via Only Ultra-short ICB in CSCC
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cutaneous Squamous Cell Carcinoma (CSCC)
Cutaneous Squamous Cell Cancer
Cutaneous Squamous Cell Carcinoma of the Head and Neck
Cutaneous Squamous Cell Carcinoma
Keywords: nivolumab
opdivo
ipilimumab
yervoy
immunotherapy
intravenous
checkpoint inhibitors
neoadjuvant
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: Erasmus Medical Center
name: Maastricht University Medical Center
name: Amsterdam UMC, location VUmc
First posted: 2025-02-12
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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. If a patient is a non-responder to immunotherapy, they will receive standard of care surgery (w/wo radiotherapy).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Rate of clinical complete remission after only immunotherapy
timeFrame: From the start of immunotherapy until 24 months of follow-up
Secondary outcomes:
measure: Rate of clinical complete remission after only immunotherapy
timeFrame: From the start of immunotherapy until 12 and 18 months of follow-up.
measure: Immune-related adverse events
timeFrame: From the start of immunotherapy until 100 days after the last course of immunotherapy.
measure: Health-related quality of life (EORTC QLQ-C30)
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Health-related quality of life (EORTC QLQ-H&N35)
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Health-related quality of life (EQ5D)
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Health-related quality of life (CWS)
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Health-related quality of life (IT)
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Health-related quality of life (sexuality questionnaire)
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Treatment duration
timeFrame: From the start of immunotherapy until the end of treatment (average 6 weeks)
measure: Treatment stops
timeFrame: From the start of immunotherapy until the end of treatment (average 6 weeks)
measure: Disease-specific survival
timeFrame: From the start of immunotherapy until 2 years follow-up.
measure: Recurrence-free survival
timeFrame: From the start of immunotherapy until 2 years follow-up.
measure: Event-free survival
timeFrame: From the start of immunotherapy until 2 years follow-up.
measure: Overall survival
timeFrame: From the start of immunotherapy until 2 years follow-up.
measure: Healthcare consumption
timeFrame: From the start of immunotherapy until 24 months of follow-up.
measure: Cost-effectiveness
timeFrame: From the start of immunotherapy until 24 months of follow-up.
Other outcomes:
measure: Tumor micro-environment (IHC)
timeFrame: From enrollment until week 5
measure: Tumor micro-environment (RNAseq)
timeFrame: From enrollment until week 5
measure: Tumor micro-environment (spatial mass cytometry)
timeFrame: From enrollment until week 5
measure: Immune dynamics (PBMC)
timeFrame: From enrollment until week 5
measure: Immune dynamics (TCR)
timeFrame: From enrollment until week 5
measure: ctDNA
timeFrame: From enrollment until week 5.
measure: Complement activation
timeFrame: From enrollment until week 5
measure: Humoural immunity
timeFrame: From enrollment until week 5
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
state: Limburg
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: The Netherlands Cancer Institute
name: Lotje Zuur, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: