Pembrolizumab as adjuvant therapy for resectable high-risk LA cSCC
- Conditions
- Resectable high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC)MedDRA version: 21.0Level: PTClassification code 10041823Term: Squamous cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001974-76-DE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 570
1. 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)
2. 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
b. Any type of neck dissection(s)
c. Any type of parotidectomy (superficial, total, partial)
3. Participant must have histologically confirmed LA cSCC with a highrisk feature(s) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary
cancer is not permitted).
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.
4. Participant must have completed adjuvant RT for LA cSCC with last dose of RT =4 weeks and =16 weeks from randomization
5. Participant must have completed at least 45 Gy of adjuvant RT for LA cSCC prior to study entry
6. Participant is disease-free as assessed by the investigator with complete radiographic staging assessment =28 days from randomization
7. Participant is male or female and at least 18 years of age at the time of signing the informed consent
8. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis),during the intervention period and for at least 120 days after the last dose of study intervention The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
1. Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
2. 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
3. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. 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
4. 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)
5. Has received prior systemic anticancer therapy including investigational agents for cSCC within 4 weeks before the start of study
intervention
6. Participant must have recovered from all radiation-related toxicities and not have had radiation pneumonitis
7. 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
8. Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
9. 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
10. Known additional malignancy that is progressing or has required active treatment the past 2 years
11. Has known active central nervous system metastases and/or carcinomatous meningitis
12. Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients
13. Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
14. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
15. Has an active infection requiring systemic therapy
16. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
17. 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
18. 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
19. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
20. 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
21. Has had an allogeneic tissue/solid organ transplant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the recurrence-free survival (RFS), as assessed by the investigator and confirmed by biopsy, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy;Secondary Objective: 1. To compare overall survival (OS) in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy<br>2. To compare mean change from baseline in health-related quality of life (HRQoL) scores from the European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy<br>3. To determine the safety and tolerability of pembrolizumab as adjuvant therapy in study participants<br>;Primary end point(s): Recurrence-free survival (RFS) as assessed by the investigator and confirmed by biopsy;Timepoint(s) of evaluation of this end point: Up to approximately 60 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Overall Survival (OS)<br>2. Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score<br>3.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<br>4. Percentage of participants who experience an adverse event (AE) <br>5. Percentage of participants who discontinue study treatment due to an adverse event (AE);Timepoint(s) of evaluation of this end point: 1. Up to approximately 60 months<br>2. Baseline and up to approximately 60 months<br>3. Baseline and up to approximately 60 months<br>4. Up to approximately 63 months<br>5. Up to approximately 38 months