A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants with High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC)(MK-3475-630/KEYNOTE-630)

Studio Clinico

Patologia: Tumori cutanei non melanoma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Adiuvante/neoadiuvante

Criteri di inclusione: 

- Participant must have histologically confirmed cSCC as the primary site of malignancy (metastatic skin involvement from another type of primary cancer or from an unknown primary cancer is not permitted).
- Participant must have undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided. Surgery may consist of 1 or a combination of the following:
    a. Resection of the primary lesion (Note: If a primary lesion is present, it must be
completely resected as above)
    b. Any type of neck dissection(s)
    c. Any type of parotidectomy (superficial, total, partial)
- Participant must have histologically confirmed LA cSCC with a high-risk feature(s) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted) [National Comprehensive Cancer Network 2017]. High-risk features include at least 1 of the following:
    a) Histologically involved nodal disease with the following features:
extracapsular extension with either at least 1 lymph node >2 cm in greatest diameter or ≥2 lymph nodes involved.
    b) Any index tumor with ≥2 of the following high-risk features:
Tumor ≥4 cm with a depth >6 mm or invasion beyond subcutaneous fat
Multifocal perineural invasion for nerves of <0.1 mm diameter (3 or more foci) or any involved nerve ≥0.1 mm diameter
Poor differentiation and/or sarcomatoid and/or spindle cell histology
Recurrent disease (any cSCC that recurs within 3 years in the previously
surgically or topically treated area)
Satellite lesions (satellitosis) and/or in-transit metastases.
Lymphatic or vascular involvement
    c) Any gross cortical bone invasion or skull base invasion and/or skull base foramen invasion.
- Participant must have completed adjuvant RT for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization.
- Participants who received an adequate post op dose of RT (either hypofractionated or conventional) are eligible. This includes all participants with a BED EQD2 >48 Gy.
Examples of commonly used acceptable regimens include doses of 30-35Gy in 5fx; 40Gy/10 fx; 40-45Gy/15fx; 50-55Gy/20fx; 45-50Gy/25fx; 50.4Gy/28fx; 54Gy/30fx; 60- 66Gy/30-33fx; the specific treatment must comply with ASTRO and RCR guidelines for adjuvant RT of high-risk LA cSCC [Likhacheva, A., et al 2020] [The Royal College of Radiologists 2019].
- Participant is disease-free as assessed by the investigator with complete radiographic
staging assessment ≤28 days from randomization.
- Participant is male or female and at least 18 years of age at the time of signing the
informed consent.

Criteri di esclusione: 

- Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization.
- Has any other histologic type of skin cancer other than invasive cSCC, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen’s disease, MCC, melanoma.
- A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment (see Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another costimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- Has received prior systemic anticancer therapy including investigational agents for cSCC within 4 weeks before the start of study intervention.
Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
- Participant must have recovered from all radiation-related toxicities and not have had radiation pneumonitis.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Administration of killed vaccines are allowed.
- Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Known additional malignancy that is progressing or has required active treatment within the past 2 years.
- Has known active central nervous system metastases and/or carcinomatous meningitis.
- Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstances that might confound the results of the study, interfere with the participant's participation for the full duration of the study such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
Other Exclusions
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
- Has had an allogeneic tissue/solid organ transplant.

Numero di pazienti previsti: 

20 in Italia

Schema di trattamento: 

Pembrolizumab/Placebo IV400mg Q6W up to 9 cycles

Trattamento sperimentale: 

Pembrolizumab

Trattamento di controllo: 

Placebo

Obiettivi primari dello studio: 

- Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy [ Time Frame: Up to approximately 60 months ].

Obiettivi secondari dello studio: 

- Overall Survival (OS) [ Time Frame: Up to approximately 60 months ];
- Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score [ Time Frame: Baseline and up to approximately 60 months ];
- Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score [ Time Frame: Baseline and up to approximately 60 months ];
- Percentage of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 63 months ];
- Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 38 months ].

Data di inizio dell'arruolamento: 01.04.2019

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2018-001974-76

Data di inserimento: 20.09.2019

Data di aggiornamento: 20.11.2023

Promotore

Merck Sharp & Dohme Corp.

CRO

NA

Principal Investigator ITALIA

Istituto Europeo di Oncologia, Milano

Riferimento: Prof.ssa Paola Queirolo

Telefono: 0257489459

Email: Paola.queirolo@ieo.it

Localita: Milano