Advanced Cutaneous Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma (CSCC), Metastatic Cutaneous Squamous Cell Carcinoma
Conditions
Keywords
CSCC, Cutaneous Squamous Cell Carcinoma, D-Dimer, Cemiplimab, PD-1 inhibitor, immunotherapy, biomarker, disease control, coagulation, real-word evidence
Brief summary
D-TECT is a prospective, multicenter, non-interventional observational study investigating whether pretreatment D-dimer levels predict disease control in patients with locally advanced or metastatic cutaneous squamous cell carcinoma treated with cemiplimab in routine clinical care. D-dimers are routinely available laboratory markers related to activation of the coagulation system. Previous single-center data suggest that elevated pretreatment D-dimer levels may be associated with poorer disease control under cemiplimab. In D-TECT, a single pretreatment D-dimer value and prospectively collected routine clinical follow-up data will be analyzed to validate this association in a multicenter real-world setting. No study-specific treatment decisions, imaging procedures, or additional blood draws are mandated by the study.
Detailed description
Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. While most cases can be treated with curative local therapy, a subgroup of patients develops locally advanced or metastatic disease requiring systemic treatment. Cemiplimab, a PD-1 inhibitor, is an established systemic treatment option for advanced cSCC. However, validated routine biomarkers predicting disease control under cemiplimab are lacking. D-dimers are fibrin degradation products and sensitive markers of coagulation activation. In a prior single-center retrospective analysis, elevated pretreatment D-dimer levels were associated with lower disease control, lower objective response, and shorter progression-free survival in patients with advanced cSCC treated with cemiplimab. D-TECT is designed to prospectively validate this observation in a multicenter real-world cohort. Eligible patients are adults with histologically confirmed locally advanced or metastatic cSCC for whom cemiplimab treatment is planned as part of routine clinical care. A D-dimer measurement is documented within 7 days before the first cemiplimab dose up to the day of first administration before infusion. Subsequent clinical data, including tumor response, progression, survival, treatment discontinuation, and thromboembolic events, are collected from routine medical records during follow-up. The primary endpoint is disease control within the first 6 months after initiation of cemiplimab. The primary confirmatory analysis compares disease control between patients with high versus low pretreatment D-dimer values using the prespecified cutoff of 0.91 mg/L FEU derived from the prior single-center study. If the primary analysis is statistically significant, the same primary endpoint will be tested hierarchically using the local laboratory-defined upper limit of normal. Additional analyses include objective response rate, progression-free survival, overall survival, thromboembolic events, diagnostic performance measures of the predefined cutoffs, sensitivity analyses, and exploratory analyses addressing inter-site assay heterogeneity.
Interventions
OTHERPretreatment D-dimer status
Pretreatment D-dimer status is defined using a single D-dimer measurement obtained in routine clinical laboratory testing within 7 days before the first cemiplimab dose up to the day of first administration before infusion. D-dimer status is not used to assign treatment and does not mandate any study-specific diagnostic or therapeutic intervention.
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma * Planned initiation of systemic treatment with cemiplimab as part of routine clinical care * Pretreatment D-dimer measurement performed within 7 days before initiation of cemiplimab treatment up to the day of first administration before infusion * Age 18 years or older at the time of consent * ECOG performance status 0 to 2 * Written informed consent for study participation and pseudonymized collection and analysis of clinical and laboratory data
Exclusion criteria
* Prior treatment with immune checkpoint inhibitors in curative or palliative intent for cutaneous squamous cell carcinoma * Concurrent second malignancy requiring systemic treatment, such as chemotherapy, immunotherapy, or targeted therapy * Clinically unstable comorbidity, including NYHA class III-IV heart failure or active systemic infection * Acute symptomatic thrombosis or pulmonary embolism within 4 weeks before the pretreatment D-dimer measurement * Incidental asymptomatic thromboembolic events detected during clinical diagnostic work-up or following an elevated D-dimer result are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate Within the First 6 Months of Cemiplimab Treatment | From start of cemiplimab treatment through 6 months | Disease control rate is defined as the proportion of participants with complete response, partial response, or stable disease according to clinical and/or radiological assessment in routine care within the first 6 months after initiation of cemiplimab. Participants with documented progression, death, or treatment discontinuation due to clinical progression within the first 6 months are considered not to have disease control. Participants without documented progression or death but without evaluable clinical or radiological follow-up assessment within the first 6 months are considered not evaluable for the primary analysis. The primary confirmatory analysis compares disease control between participants with high versus low pretreatment D-dimer levels using the prespecified cutoff of 0.91 mg/L FEU. If statistically significant, the same primary endpoint will be tested hierarchically using the local laboratory-defined upper limit of normal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From start of cemiplimab treatment through 24 months | Objective response rate is defined as the proportion of participants with complete response or partial response according to clinical and/or radiological assessment in routine care during follow-up. |
| Progression-Free Survival | From start of cemiplimab treatment through 24 months | Progression-free survival is defined as the time from initiation of cemiplimab treatment to the first documented disease progression or death from any cause, whichever occurs first. |
| Overall Survival | From start of cemiplimab treatment through 24 months | Overall survival is defined as the time from initiation of cemiplimab treatment to death from any cause. |
| Thromboembolic Events During Follow-up | From start of cemiplimab treatment through 24 months | Incidence of venous or arterial thromboembolic events documented during follow-up and evaluated in relation to pretreatment D-dimer levels. |
| Diagnostic Performance of Prespecified D-dimer Cutoffs for 6-Month Disease Control | From start of cemiplimab treatment through 6 months | Sensitivity, specificity, positive predictive value, and negative predictive value of the prespecified D-dimer cutoff of 0.91 mg/L FEU and of the local laboratory-defined upper limit of normal for disease control within the first 6 months after initiation of cemiplimab. |
Countries
Austria, Germany
Contacts
CONTACTGlenn Geidel, MD, MSc
PRINCIPAL_INVESTIGATORGlenn Geidel, MD, MSc
Universitätsklinikum Hamburg-Eppendorf
Outcome results
None listed