Towards Cure Via Only Ultra-short ICB in CSCC (MATISSE 2)

May 22, 2025 updated by: The Netherlands Cancer Institute

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Lotje Zuur, Prof. Dr.
  • Phone Number: +31205129111
  • Email: c.zuur@nki.nl

Study Contact Backup

  • Name: Stan W. van Dijk, MD
  • Phone Number: +31205129111
  • Email: matisse2@nki.nl

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3584CX
        • Not yet recruiting
        • UMC Utrecht
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229HX
        • Not yet recruiting
        • Maastricht UMC
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1105AZ
        • Not yet recruiting
        • Amsterdam UMC
      • Amsterdam, Noord-Holland, Netherlands, 1066CX
        • Recruiting
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3015GD
        • Not yet recruiting
        • Erasmus MC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Neoadjuvant nivolumab + ipilimumab
Intravenous neoadjuvant nivolumab 3 mg/kg in week 0 and 2 in combination with intravenous neoadjuvant ipilimumab 1 m/kg in week 0.
Drug: Nivolumab
3 mg/kg
Other Names:
  • Immunotherapy
Drug: Ipilumimab
1 mg/kg
Other Names:
  • Immunotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of clinical complete remission after only immunotherapy
Time Frame: From the start of immunotherapy until 24 months of follow-up
The rate of patients with a clinical complete remission at 24 months of follow-up or at time of death prior to 24 months follow-up, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy.
From the start of immunotherapy until 24 months of follow-up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of clinical complete remission after only immunotherapy
Time Frame: From the start of immunotherapy until 12 and 18 months of follow-up.
The rate of patients with a clinical complete remission at 12 and 18 months of follow-up or at time of death prior to the specified time-point, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy
From the start of immunotherapy until 12 and 18 months of follow-up.
Immune-related adverse events
Time Frame: From the start of immunotherapy until 100 days after the last course of immunotherapy.
The rate and type of immune-related adverse events (CTCAE v5.0, Clavien-Dindo).
From the start of immunotherapy until 100 days after the last course of immunotherapy.
Health-related quality of life (EORTC QLQ-C30)
Time Frame: From the start of immunotherapy until 24 months of follow-up.
EORTC Core Quality of Life questionnaire. Rated on a Likert-type scale from one (never) to four (almost always), to evaluate different domains. Functional and global health status scales indicated towards better levels of functioning, whereas higher scores in the symptom scales demonstrated higher levels of symptoms.
From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EORTC QLQ-H&N35)
Time Frame: From the start of immunotherapy until 24 months of follow-up.
EORTC Head and Neck Cancer Quality of Life Questionnaire. Rated on a Likert-type scale from one (never) to four (almost always). Multi-item scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality), and six symptom items (dental problems, opening mouth, dry mouth, sticky saliva, coughing, and feeling ill). Higher scores in the symptom scales demonstrated higher levels of symptoms.
From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EQ5D)
Time Frame: From the start of immunotherapy until 24 months of follow-up.
EuroQol Five Dimensions Health Questionnaire. Domains: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. It also includes a VAS regarding patients' "Health Today" scored between 0 and 100. Each domain will be converted into categorical values (problems vs no problems).
From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (CWS)
Time Frame: From the start of immunotherapy until 24 months of follow-up.
Cancer worry scale. Rated on a Likert-type scale from one (never) to four (almost always), which were summed to produce a total CWS score ranging from 8 to 32, with higher scores indicating more frequent worries about cancer.
From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (IT)
Time Frame: From the start of immunotherapy until 24 months of follow-up.
Immunotherapy questionnaire. Rated on a Likert-type scale from one (never) to four (almost always), to evaluate toxicity after immunotherapy treatment.
From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (sexuality questionnaire)
Time Frame: From the start of immunotherapy until 24 months of follow-up.
Rated on a Likert-type scale from one (never) to four (almost always), to evaluate problems in sexual functioning.
From the start of immunotherapy until 24 months of follow-up.
Treatment duration
Time Frame: From the start of immunotherapy until the end of treatment (average 6 weeks)
Total duration of received treatment
From the start of immunotherapy until the end of treatment (average 6 weeks)
Treatment stops
Time Frame: From the start of immunotherapy until the end of treatment (average 6 weeks)
The amount of times and the length of time the immunotherapy, surgery or adjuvant radiotherapy had to be stopped.
From the start of immunotherapy until the end of treatment (average 6 weeks)
Disease-specific survival
Time Frame: From the start of immunotherapy until 2 years follow-up.
The length of time a patient survives without death due to disease.
From the start of immunotherapy until 2 years follow-up.
Recurrence-free survival
Time Frame: From the start of immunotherapy until 2 years follow-up.
The length of time a patient survives without recurrent disease.
From the start of immunotherapy until 2 years follow-up.
Event-free survival
Time Frame: From the start of immunotherapy until 2 years follow-up.
The length of time a patient survives without recurrent disease or death of any cause.
From the start of immunotherapy until 2 years follow-up.
Overall survival
Time Frame: From the start of immunotherapy until 2 years follow-up.
The length of time a patient survives after treatment.
From the start of immunotherapy until 2 years follow-up.
Healthcare consumption
Time Frame: From the start of immunotherapy until 24 months of follow-up.
Healthcare consumption during the trial.
From the start of immunotherapy until 24 months of follow-up.
Cost-effectiveness
Time Frame: From the start of immunotherapy until 24 months of follow-up.
The incremental cost-effectiveness ratio between quality-adjusted life years and the cost of trial-related healthcare.
From the start of immunotherapy until 24 months of follow-up.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tumor micro-environment (IHC)
Time Frame: From enrollment until week 5
Temporal and spatial analyses of the TME in the lymph nodes and primary tumours will be explored using immunohistochemistry (e.g. PD-L1 expression, CPS score).
From enrollment until week 5
Tumor micro-environment (RNAseq)
Time Frame: From enrollment until week 5
Temporal and spatial analyses of the TME in the lymph nodes and primary tumours will be explored using bulk and single-cell RNA-sequencing.
From enrollment until week 5
Tumor micro-environment (spatial mass cytometry)
Time Frame: From enrollment until week 5
Temporal and spatial analyses of the TME in the lymph nodes and primary tumours will be explored using spatial mass cytometry.
From enrollment until week 5
Immune dynamics (PBMC)
Time Frame: From enrollment until week 5
Temporal immune dynamics in peripheral blood will be investigated via peripheral blood mononuclear cells (PBMCs).
From enrollment until week 5
Immune dynamics (TCR)
Time Frame: From enrollment until week 5
Temporal immune dynamics in peripheral blood will be investigated via TCR analyses of peripheral immune cells in comparison to intratumoural immune cells
From enrollment until week 5
ctDNA
Time Frame: From enrollment until week 5.
The ctDNA in peripheral blood using CyclomicsSeq
From enrollment until week 5.
Complement activation
Time Frame: From enrollment until week 5
Complement activation, complement mediated neutrophil activation in the TME and their contribution on the immune response during neoadjuvant immunotherapy
From enrollment until week 5
Humoural immunity
Time Frame: From enrollment until week 5
Activation of humoral immunity, and specifically treatment-induced changes in antibody production and their relation with treatment response
From enrollment until week 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Netherlands Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Maastricht University Medical Center
UMC Utrecht
Erasmus Medical Center
Amsterdam UMC, location VUmc

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lotje Zuur, Prof. Dr., The Netherlands Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 14, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 12, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M24MAT
  • 2024-516152-17-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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