Validation of Molecular Diagnostic Assays to Detect Cancer Biomarkers in Blood and Primary Tumor in HNSCC/NSCLC/Melanoma

A Clinical Performance Study to Validate the Use of Novel Molecular Diagnostic Assays for the Detection of Cancer Biomarkers in Peripheral Blood and Primary Tumor Tissue of Patients With Recurrent/Metastatic HNSCC, NSCLC or Melanoma.

Conventional biopsy and surgical tumor resection are invasive procedures that capture only one instance of the progression of the tumor. However, the genome of tumor is not static, but it is constantly altered during treatment.

Liquid biopsy is a non-invasive approach based on the extraction of information through peripheral blood analysis. It makes it possible to characterize the development of a solid tumor in real time, through detailed molecular analysis of circulating genetic material in peripheral blood.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Diagnostic test: PD-L1 Kit

Detailed Description

Conventional biopsy and surgical tumor resection are invasive procedures that capture only one instance of the progression of the tumor. However, the genome of tumor is not static, but it is constantly altered during treatment.

Liquid biopsy is a non-invasive approach based on the extraction of information through peripheral blood analysis. It makes it possible to characterize the development of a solid tumor in real time, through detailed molecular analysis of circulating genetic material in peripheral blood.

Study procedure:

1. Initial Visit (V0-Baseline): For the purposes of the study the following information will be collected: the demographics, medical and social history, the characteristics of the disease (stage, molecular characterization e.t.c) and the treatment regimen that is followed. As part of the visit, 20 mL of peripheral blood will be drawn prior to their treatment according to physician's suggestion as per common clinical practice. Blood samples will be then sent to ACTC laboratory for plasma/CTC isolation, DNA and RNA extraction and subsequent test for biomarkers. Primary tumor tissue samples will be also collected.

2. Follow-up visit (V1): All patients will provide a 10 mL peripheral blood sample during their planned visit at the end of a series of immunotherapy cycles as per clinical practice and physician's judgment. More specifically:

   For HNSCC/NSCLC: at the end of four (4) treatment cycles with nivolumab (2 months) or at the end of three (3) treatment cycles with pembrolizumab (2 months) or on disease progress (PD) For melanoma: at 6 months after treatment initiation (antiPD-1) Blood samples will be then sent to laboratory for plasma/CTC isolation, DNA and RNA extraction and subsequent test for biomarkers. Clinical response (CR, PR, SD, PD) will be also documented.

3. Follow-up visit (V2): All patients will provide a 10 mL peripheral blood sample on progress of the disease or at the end of the observation period, as diagnosed during their planned visit as per clinical practice and physician's judgment. Blood samples will be then sent to laboratory

• Study Type: Observational
• Enrollment (Anticipated): 185

Contacts and Locations

Study Locations

• Greece
  • Alexandroupolis, Greece, 68100
    • University General Hospital of Alexandroupoli
  • Piraeus, Greece, 18547
    • Metropolital Hospital
  • Attica
    • Athens, Attica, Greece, 11528
      • Aretaieio University Hospital of Athens
    • Athens, Attica, Greece, 11527
      • Sotiria Thoracic Diseases Hospital of Athens
  • Attika
    • Athens, Attika, Greece, 124 62
      • University General Hospital of Athens Attikon
  • Thessaloniki
    • Thessaloníki, Thessaloniki, Greece, 546 22
      • Bioclinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

155 subjects as follows: 25 patients with metastatic/recurrent HNSCC 120 patients with metastatic NSCLC 10 patients with metastatic melanoma 30 healthy subjects

Description

Inclusion Criteria:

1. Male or female aged ≥ 18 years of age.

2. Patients with a diagnosis of

   1. recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), who are going to receive PD-1 inhibitor nivolumab OR
   2. metastatic Non-Small Cell Lung Cancer (NSCLC), who are going to receive PD-1 inhibitor, e.g. nivolumab, pembrolizumab,OR
   3. metastatic melanoma, who are going to receive to receive PD-1 inhibitor, e.g. nivolumab, pembrolizumab.
3. Available tumor tissue sample for immunohistochemical and molecular analysis.
4. Life expectancy ≥ 4 months.
5. Signed informed consent form.

Exclusion Criteria:

1. Male or female younger than 18 years old.
2. History of another malignancy within 3 years or current 2nd primary malignancy.
3. Patients that have not signed the informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HNSCC, NSCLC, melanoma Patients; The study population are subjects with a confirmed diagnosis of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), who are going to receive PD-1 inhibitor nivolumab or ii) metastatic Non-Small Cell Lung Cancer (NSCLC), who are going to receive PD-1 inhibitor, e.g. nivolumab, pembrolizumab or iii) metastatic melanoma, who are going to receive PD-1 inhibitor, e.g. nivolumab, embrolizumab. The selected inclusion/exclusion criteria have been set to include in the performance study appropriate population of interest, as broad as possible, but to exclude these subjects that have another current malignancy or any history of recent malignancy within 3 years.	Diagnostic test: PD-L1 Kit; Clinical performance of PD-L1 kit in CTCs of peripheral blood and tumor tissue samples
Healthy volunteers; In case of healhty volunteers, only peripheral blood samples will be collected.	Diagnostic test: PD-L1 Kit; Clinical performance of PD-L1 kit in CTCs of peripheral blood and tumor tissue samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical performance of PD-L1 kit in CTCs of peripheral blood and tumor tissue samples	The performance of PD-L1 kit at baseline in CTCs (using IF as reference method) and tumor tissue samples (using IHC as reference method) will be assessed via Sensitivity, Specificity, Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study correlations between PD-L1 expression in serial liquid samples with patients' responsiveness to therapy.	Clinical response to the selected treatment (CR, PR, SD, PD); Survival status	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study mutation status of BRAF gene in tumor tissue samples and blood samples (CTC, plasma ctDNA) of metastatic melanoma patients	Mutation profile of BRAF in CTCs, plasma-ctDNA and tumor tissues of metastatic melanoma patients will be evaluated using PCR-molecular assays	18 months
To study the presence of biomarkers in tumor tissue and blood liquid biopsy samples (at baseline).	Molecular profile of cancer biomarkers in tumor tissue and peripheral blood samples will be evaluated using PCR-molecular assays	18 months

Collaborators and Investigators

• Sponsor: Pharmassist Ltd
• Collaborators: University of Athens

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Anticipated): May 25, 2023
• Study Completion (Anticipated): June 25, 2023

Study Registration Dates

• First Submitted: February 20, 2020
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: PD-L1; Liquid biopsy; CTC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Carcinoma, Squamous Cell; Melanoma; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: CBS-PD-L1a

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No