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Cutaneous Squamous Cell CarcinomaPhase 2MATISSENCT04620200

Neo-adjuvant Nivolumab or Nivolumab With Ipilimumab in Advanced Cutaneous Squamous Cell Carcinoma Prior to Surgery

A Phase 2 study testing Nivolumab and Ipilimumab in people with Cutaneous Squamous Cell Carcinoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To determine the histopathological response rate to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of standard of care(surgery ± radiotherapy).in patients with cutaneous squamous cell carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cutaneous Squamous Cell Carcinoma
What is being tested?
Nivolumab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteNetherlands
Study dates
11 Aug 2020to 7 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years or older.
  • Patient is able to understand and comply with the protocol requirements and has signed the informed consent form.
  • World Health Organization (WHO) Performance Status 0 or 1 (Appendix B).
  • Patients with histologically or cytologically confirmed, primary or recurrent stage III-IVA CSCC of all body sites.
  • OR
  • Patients with histologically or cytologically proven stage I-II CSCC, only in the case of:
Show all 13Show fewer
  • Presence of multifocal disease for which extensive and/or mutilating surgery is necessary (e.g. near-total scalp resection).
  • Situated in an anatomical localization that necessitates extensive and/or mutilating surgery (e.g. orbital exenteration).
  • Eligible for standard-of-care, curatively intended surgery with or without adjuvant radiotherapy.
  • Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109 /L, Neutrophils ≥1.5x109 /L, Platelets ≥100 x109 /L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN (except subjects with Gilbert Syndrome, who are eligible when total bilirubin < 3.0 mg/dL).
  • Women of childbearing 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 for nivolumab to undergo five half-lives) after the last dose of the investigational drug.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of nivolumab or nivolumab + ipilimumab.
  • Men who are sexually active with WOCBP must use a contraceptive method with a failure rate of less than 1% per year and will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Surgically sterile or azoospermic men do not require aforementioned contraception.

Who cannot join

  • Distantly metastasized (stadium IVb) CSCC.
  • SCC localized in a mucosal surface (i.e. anus, vulva, penis or mucosal portion of lip).
  • Patients for whom SOC consists of definitive (brachy)radiotherapy.
  • Primary or recurrent CSCC appearing in an area that has been previously irradiated.
  • Prior anti-CTLA4 or anti-PD1 immunotherapy.
  • Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Show all 19Show fewer
  • A 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 for:
  • 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 study drug hazardous or obscure the interpretation of toxicity or AE.
  • A concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids;
  • Pregnant or nursing.
  • A history of allergy to study drug components and/or a 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.
  • Use of prohibited medication at start of study period

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • NKI-AVL

    Amsterdam, North Holland, 1066CX

Other trials in Netherlands

About this study

Official title: Neo-adjuvant Nivolumab or Nivolumab With Ipilimumab in Advanced Cutaneous Squamous Cell Carcinoma Patients Prior to Standard of Care Surgery; the MATISSE Trial

To determine the histopathological response rate to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of standard of care(surgery ± radiotherapy).in patients with cutaneous squamous cell carcinoma.

Read the detailed description

This is an investigator-initiated randomized non-comparative phase II trial consisting of 40 patients with resectable stage III-IVa CSCC randomized 1:1 to ARM A: 2 courses of nivolumab 3 mg/kg in week 0 and 2, or ARM B: 2 courses of nivolumab 3 mg/kg in week 0 and 2 plus 1 course of ipilimumab 1mg/kg in week 0. Both treatment arms are neo-adjuvant and applied prior to standard of care (consisting of surgery at week 4 with or without adjuvant radiotherapy).

Being tested
Nivolumab, Ipilimumab
Keywords
immunotherapy, neoadjuvant, nivolumab, ipilimumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04620200
Study groupRoleWhat they receive
ARM AExperimental2 courses of nivolumab 3 mg/kg in week 0 and 2 prior to standard of care
Receives: Drug: Nivolumab
ARM BExperimental2 courses of nivolumab 3 mg/kg in week 0 and 2 plus 1 course of ipilimumab 1mg/kg in week 0 prior to standard of care
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Histopathological response rate at standard of care

    The proportion of viable tumor cells left in the resected specimen, to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of SOC (surgery ± RT).

    Measured: At time of standard of care at week 4

Secondary outcomes (12)

  1. Sensitivity and specificity of tumor biopsies, clinical photography, FDG-PET and (functional)MRI compared to the histopathological tumor response to neo-adjuvant immunotherapy

    Histopathological tumor response to neo-adjuvant immunotherapy as measured in the tumor resection specimen will be compared to the tumor response as measured via serial tumor biopsies, the tumor biopsy at time of surgery and imaging (clinical photography, FDG-PET and (f)MRI). Histopathologic response in the tumor biopsies will be defined similarly as histopathologic response in the resected specimen. Response at imaging studies will be measured as follows: Clinical photography via specific clinical observation criteria, FDG-PET via RECIST 1.1 criteria and % change in TLG or MTV and (f)MRI via RECIST 1.1

    Measured: At time of standard of care at week 4

  2. Numbers of participants without significant delay (>1 week) or cancelation of SOC surgery due to immune-related toxicity

    Measured: At time of standard of care at week 4

  3. Recurrence free survival (RFS) at 2 years FU of responders versus non-responders to neo-adjuvant ICI

    Measured: At 2-years follow up

  4. Overall survival (OS) at 2 years FU of responders versus non-responders to neo-adjuvant ICI

    Measured: At 2-years follow up

  5. The number of patients with AE (rate and type) acoording to NCI CTCAE v.5.0 up to 2 years FU after SOC

    Measured: At 2-years follow up

  6. Clinical response of potentially additional AK surface areas after ICI identified by digital clinical photography on day 0, day 14, day 28 and every 6 months during FU up to 2 years.

    Measured: On day 0, day 14, day 28 (at time of surgery) and every 6 months during FU up to 2 years.

  7. Quality of life as measured by EORTC QLQ-C30

    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.

    Measured: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU

  8. Quality of life as measured by H&N 35

    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 (teeth problems, opening mouth, dry mouth, sticky saliva, coughing, and feeling ill). Higher scores in the symptom scales demonstrated higher levels of symptoms.

    Measured: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU

  9. Quality of life as measured by the EQ5D,

    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).

    Measured: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU

  10. Quality of life as measured by the cancer worry scale (CWS)

    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.

    Measured: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU

  11. Quality of life as measured by the IT questionnaire

    Rated on a Likert-type scale from one (never) to four (almost always), to evaluate toxicity after immunotherapy treatment.

    Measured: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU

  12. Quality of life as measured by the sexuality questionnaire

    Rated on a Likert-type scale from one (never) to four (almost always), to evaluate problems in sexual functioning.

    Measured: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2020
  2. Study start11 Aug 2020
  3. Primary completion7 Jan 2025
  4. Study completion7 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04620200
Sponsor's protocol ID
N20MAT
Acronym
MATISSE
Status last verified
Aug 2025
First submitted
20 Aug 2020
Last updated
11 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Data will not be transferred.

Publications

  • Breukers SE, Traets JJH, van Dijk SW, Ostos MM, Fraterman I, Crommelin RD, van der Hulst H, Qiao X, Boere T, van de Poll-Franse LV, Retel V, van der Noort V, Vos JL, Toppenberg AGL, van der Heijden M, Missale F, Balm F, van den Brekel M, Dirven R, Karakullukcu MB, Karssemakers L, Klop WMC, Lohuis PJFM, Schreuder WH, Smeele LE, van der Velden LA, Plasmeijer E, Smit LA, de Boer JP, Navran A, Westerink B, de Koekkoek-Doll PK, Castelijns J, Wondergem M, Vogel WV, Kuijpers A, van Houdt WJ, Onderwater S, Maas-Bannink E, Cornelissen S, Broeks A, Tijink BM, Devriese LA, de Bree R, Blank CU, Schumacher TN, Thommen DS, Haanen JBAG, Zuur CL. Neoadjuvant ipilimumab and nivolumab in resectable cutaneous squamous cell carcinoma: a randomized phase 2 trial. Nat Med. 2025 Dec;31(12):4055-4064. doi: 10.1038/s41591-025-03943-w. Epub 2025 Oct 8.

    PubMed 41062829

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Ipilimumab in people with Cutaneous Squamous Cell Carcinoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Histopathological response rate at standard of care (time frame: At time of standard of care at week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04620200, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.

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