Effects of Genomic Profiles on Thromboembolic Risk in Patients With Locally Advanced or Metastatic Non-small-cell Lung Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University Of Perugia
- Enrollment
- 500
- Locations
- 1
- Primary Endpoint
- Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1and soluble P-selectin
Study Overview
Brief Summary
Multicenter, prospective observational study (15 Oncologic Centers, in Italy). The purpose of the study is to assess the thromboembolic potential in patients with oncogene-addicted and wild-type NSCLC. The primary aim of this project is to evaluate the association between oncogene mutations and levels of plasma parameters of the activated coagulation cascade as the plasma levels of TF, thrombin generation, IL 6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin in NSCLC patients. A total of 500 NSCLC patients with a diagnosis (cytologically or histologically confirmed) of locally advanced or metastatic disease will be enrolled in the study, with a ratio of 1:1 for oncogene addicted or wild-type group. The oncogene-addicted group (Group A): patients with at least one oncogene mutation (i.e., patients expressing EGFR mutations, KRAS mutation, ALK or ROS1 rearrangements); the wild type group (Group B): patients without oncogene mutations, categorized in 2 subgroups according to expression of PD1/PD-L1 mutation or not. Patients will be followed up prospectively for 6 months or until death, VTE event, loss to follow-up, or voluntary consent withdrawal.
This study will evaluate the effects of EGFR, KRAS mutations and ALK/ROS 1 and PD-1/PD-L1 rearrangements on the expression of TF and thrombin generation or the interaction between inflammation and endothelial or platelet and cancer cells, in patients with NSCLC. The study will also evaluate the potential correlation between VTE events and the expression of oncogene mutations in patients with NSCLC.
The results of this study could generate the hypothesis of including the genetic profile as variable for a risk-stratification tools and decision-making algorithms in NSCLC patients.
Detailed Description
The primary outcome is to determine the levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin in patients with NSCLC before starting the new line of anticancer therapy and after 3 and 6 months of anticancer treatment, across different patterns and association of oncogene mutations.
The further endpoints of the study will be to evaluate:
- Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin across different cancer stages and oncogene profile;
- The potential correlation between VTE events with Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin;
- VTE risk across different patterns of oncogene mutations in NSCLC patients;
- Role of combined strategies including clinical patients' features, Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin and oncogene mutations to assess the risk of VTE in patients with NSCLC;
- Role of anticancer treatments in modifying the rate of clinically overt VTE events in patients with oncogene addicted or wild-type pattern of NSCLC,
- Analysis of survival based on oncogenic profile and Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin.
Blood sampling:
Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1, and soluble P-selectin in patients with NSCLC before starting the anticancer therapy, at 3 months, and at 6 months, or in case of clinical suspicion of symptomatic VTE event, or documented incidental proximal deep vein thrombosis, or pulmonary embolism will be collected.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •• Patients aged 18 years or older,
- •Cytological or histological confirmation of NSCLC,
- •Locally advanced or metastatic disease (Stage III-IV),
- •Patients starting a new anticancer treatment for locally advanced/metastatic disease (first or further line of treatment),
- •Testing for oncogenic (EGFR, KRAS, ALK, ROS1 and PD-1/PD-L1) profile performed,
- •Written informed consent
Exclusion Criteria
- •• Patients received surgery or radiotherapy for lung cancer within the past 3 months before recruitment or chemotherapy within the past 1 months before recruitment,
- •Patients with a history of VTE after cancer diagnosis or evidence of VTE events at enrollment
- •Continuative use of anticoagulant drugs for any indication (atrial fibrillation or previous VTE)
- •ECOG performance profile 3 or 4
- •Life expectancy of less than 3 months
Outcomes
Primary Outcomes
Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1and soluble P-selectin
Time Frame: From enrollment to the end of study period at 6 months
Levels of plasma TF, thrombin generation, IL6, vWF, ADAMTS-13 activity, PAI-1and soluble P-selectin in patients with NSCLC before the starting of the new line of anticancer therapy and after 3 and 6 months of anticancer treatment, across different patterns and association of oncogene mutations.
Secondary Outcomes
No secondary outcomes reported
Investigators
MELINA VERSO
Associate Professor
University Of Perugia