eo-adjuvant nivolumab or nivolumab with ipilimumab in advanced cutaneous squamous cell carcinoma patients prior to standard of care surgery; the MATISSE trial
- Conditions
- cutaneous squamous cell carcinoma10040900
- Registration Number
- NL-OMON52693
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 40
1. Age 18 years or older.
2. Patient is able to understand and comply with the protocol requirements and
has signed the informed consent form.
3. World Health Organization (WHO) Performance Status 0 or 1 (Appendix B).
4. Patients with histologically or cytologically confirmed, de novo/primary or
recurrent stage III-IVA CSCC (T3-4 N0-3 M0 or T0-2/x N1-3 M0) of all body
sites.
• Primary tumor sites Head and Neck:
o Vermillion border lip: C00.0, C00.1, C00.2
o Skin of lip NOS: C44.0
o External ear: C44.2
o Skin face unspecified (ao: external lip and nasal vestibulum): C44.3
o Skin scalp and neck: C44.4
o Overlapping lesion of skin: C44.8
o Primary site eyelid: C44.1
• CSCC outside head and neck area, but not vulva, anus and penis
OR
Patients with histologically or cytologically proven stage I-II CSCC (T1-2 N0
M0), only in the case of:
• 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, (partial) nose amputation or
(partial) ear amputation).
5. Eligible for standard-of-care, curatively intended surgery with or without
adjuvant radiotherapy.
6. 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).
7. 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.
8. 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.
9. 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.
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1. Distantly metastasized (stadium IVb) CSCC.
2. SCC localized in a mucosal surface (i.e. anus, vulva, penis or mucosal
portion of lip).
3. Patients for whom SOC consists of definitive (brachy)radiotherapy.
4. Primary or recurrent CSCC appearing in an area that has been previously
irradiated.
5. Prior anti-CTLA4 or anti-PD1 immunotherapy.
6. Active human immunodeficiency virus (HIV) or known acquired immunodeficiency
syndrome (AIDS).
7. A positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C
antibody (HCV Ab).
8. 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.
9. 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.
10. A concurrent medical condition requiring the use of immunosuppressive
medications, or immunosuppressive doses of systemic or absorbable topical
corticosteroids;
11. Pregnant or nursing.
12. A history of allergy to study drug components and/or a history of severe
hypersensitivity to any monoclonal antibody.
13. Use of other investigational drugs 30 days before study drug administration
and 5 half times before study inclusion.
14. Use of prohibited medication at start of study period (see paragraph 5.2).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint will be histopathological tumor response after<br /><br>neo-adjuvant ICI, defined as the proportion of viable tumor cells left in the<br /><br>resected specimen. Responses will be divided into histopathological complete<br /><br>response (pCR, no viable tumor cells), histopathological near complete response<br /><br>(near-pCR, <=10% viable tumor cells) and histopathological partial response<br /><br>(pPR, <=50% viable tumor cells). </p><br>
- Secondary Outcome Measures
Name Time Method