NCT06065592

Brief Summary

This study aims to assess biomarkers and their related polymorphisms in the context of cancer-associated thromboembolism, with a particular focus on their interaction with the immune system. The roles of immune checkpoints, inflammatory and angiogenesis factors, as well as circulating immune cells will be elucidated. Additionally, our investigation extends to the exploration of long non-coding RNAs (LncRNAs) and genes associated with the coagulation vascular system. Initially, these aspects will be evaluated in the context of colorectal cancer, with the intention to expand our research to other solid tumors. The identification of these biomarkers and genetic factors holds the potential to revolutionize therapeutic approaches for patients with cancer-associated thromboembolism, shedding light on their chemotherapy resistance. The effectiveness of combining immunotherapy with targeted inhibitors like Palbociclib and anticoagulants such as Rivaroxaban, among other potential interventions, will be assessed. This study aims to make significant contributions to the understanding of these critical aspects, ultimately leading to the development of more effective treatment strategies for cancer patients.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
500

participants targeted

Target at P75+ for phase_1 cancer

Timeline
Completed

Started Feb 2019

Longer than P75 for phase_1 cancer

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2019

Completed
4.6 years until next milestone

First Submitted

Initial submission to the registry

September 6, 2023

Completed
28 days until next milestone

First Posted

Study publicly available on registry

October 4, 2023

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2024

Completed
Last Updated

October 6, 2023

Status Verified

October 1, 2023

Enrollment Period

5.8 years

First QC Date

September 6, 2023

Last Update Submit

October 5, 2023

Conditions

Keywords

cancerthromboembolismcardiovascularimmune cellsimmunotherapychemotherapyinflammationgene polymorphismbiomarkerLncRNAPalbociclibRivaroxabanblood coagulation

Outcome Measures

Primary Outcomes (4)

  • Venous Thromboembolism (VTE) Events including: Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and other Thromboembolic Events (Vein Thrombosis, Portal Vein Thrombosis, Superior Mesenteric Vein Thrombosis, and Renal Vein Thrombosis)

    The outcome measure of VTE including DVT, PE, and other thromboembolic events will be assessed by : (1) Clinical Assessment: Clinical symptoms such as swelling and pain in the lower limbs, tenderness behind the lower leg and/or medial thigh, and supplementary evaluation with color ultrasound of the veins in both lower limbs (lower extremity venography); (2) Imaging: CT pulmonary arteriography (CTPA) will be employed in conjunction with related clinical manifestations such as dyspnea and shortness of breath for diagnosing PE; (3) Laboratory Criteria: Diagnostic criteria will also consider laboratory parameters, including elevated D-dimer levels (\> 1000 ng/mL), increased fibrinogen levels (\> 700 mg/dL), and shortened activated partial thromboplastin time (aPTT) (\< 20 sec).

    up to 60 months

  • Assessment of Cancer Progression

    The assessment of cancer progression will be conducted using the standardized TNM staging system and applying the Response Evaluation Criteria (RECIST) guideline (ver. 1.1). Clinical parameters, laboratory tests indicative of cancer progression (including tumor markers and histopathological analysis), and relevant imaging modalities (e.g., CT, MRI, or PET scans) will be employed to evaluate the extent of primary tumor growth, lymph node involvement, and the presence of distant metastases. Progression-Free Survival (PFS), a key primary clinical endpoint for assessing cancer progression, will be calculated as the duration (in months) from the date of enrollment in the study until the tumor progresses, new lesions appear, or until the participant's death from any cause. Cancer progression will be determined based on RECIST guidelines, considering an increase in tumor size or the appearance of new lesions according to imaging assessments and clinical evaluations.

    up to 60 months

  • Identification of Potential Biomarkers

    The objective of this outcome is to identify and characterize novel biomarkers associated with thromboembolism and cancer progression. Specifically, the assessment will focus on Long Non-Coding RNAs (LncRNAs) such as CDKN2B and CDKN2B-AS1, and markers related to the vascular coagulation system including ACE, PAI-1, FXIII, and Prothrombin. This identification process will involve collecting biological samples (e.g., blood, tissue) from enrolled patients at the time of study enrollment. The assessment will analyze and evaluate the expression and polymorphisms of the studied genes (CDKN2B, CDKN2B-AS1, ACE, PAI-1, FXIII, and Prothrombin) using quantitative PCR (qPCR), with Ct (Cycle threshold) as the common unit of measure for all genes. This comprehensive assessment aims to enhance our understanding of the molecular signatures linked to thromboembolism and cancer progression, illuminating potential diagnostic and therapeutic avenues for improved patient outcomes.

    Once at the moment of the patient's enrollment in the study

  • Evaluation of Treatment Response to Palbociclib

    This primary outcome assesses treatment response in patients undergoing Palbociclib therapy for controlling cancer progression and thromboembolism. The evaluation will employ RECIST criteria to measure the percentage change in tumor size, indicative of treatment effectiveness.

    up to 60 months

Secondary Outcomes (8)

  • Survival Rates

    up to 60 months

  • Examination of Genetic Variants, specifically rs1333049 G>C Polymorphism within the CDKN2B-AS1 Gene

    Once at the moment of the patient's enrollment in the study

  • Adverse Events

    up to 60 months

  • Immunophenotyping of Immune Cell Populations

    up to 60 months

  • Inflammatory Cytokine Profiling

    up to 60 months

  • +3 more secondary outcomes

Study Arms (5)

Non-Carriers of Targeted Gene-Related Polymorphisms (GRPs) in Cancer Patients

ACTIVE COMPARATOR

Cancer patients without any incidence of thromboembolism will be included if they are non-carriers of the targeted gene-related polymorphism (GRP).

Genetic: SNP

Carriers of Targeted GRPs in Cancer Patients

ACTIVE COMPARATOR

Cancer patients without any incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism.

Genetic: SNP

Carriers of Targeted GRPs in Cancer-Associated Thromboembolism Patients

EXPERIMENTAL

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism.

Genetic: SNP

Carriers of Targeted GRPs in Cancer-Associated Thromboembolism Patients Treated with Palbociclib

EXPERIMENTAL

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism and will be subjected to Palbociclib treatment.

Drug: PalbociclibGenetic: SNP

Carriers of Targeted GRPs in Cancer-Associated Thromboembolism Treated with Anti-Coagulant

EXPERIMENTAL

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism and will be subjected to anti-coagulant treatment.

Drug: RivaroxabanGenetic: SNP

Interventions

Palbociclib will be administered at a dose of 125 mg oral on a 21/7 cycle.

Also known as: Ibrance
Carriers of Targeted GRPs in Cancer-Associated Thromboembolism Patients Treated with Palbociclib

Rivaroxaban will be administered at a dosage of 15 mg intravenously twice a day for 21 days, followed by 20 mg once daily for the subsequent 21 days.

Also known as: Xarelto
Carriers of Targeted GRPs in Cancer-Associated Thromboembolism Treated with Anti-Coagulant
SNPGENETIC

diagnostics of patients' carriers or not of the risk allele(s)

Also known as: Risk Allele(s)
Carriers of Targeted GRPs in Cancer PatientsCarriers of Targeted GRPs in Cancer-Associated Thromboembolism PatientsCarriers of Targeted GRPs in Cancer-Associated Thromboembolism Patients Treated with PalbociclibCarriers of Targeted GRPs in Cancer-Associated Thromboembolism Treated with Anti-CoagulantNon-Carriers of Targeted Gene-Related Polymorphisms (GRPs) in Cancer Patients

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Individuals of white ethnicity.
  • Age between \> 18
  • Both males and females.
  • Diagnosis of selected cancer type (e.g., colorectal cancer).
  • Cancer stage 0/I/II without metastasis or lymph node dissemination at the time of enrollment.
  • No previous cancer therapy (radiotherapy, chemotherapy, or immunotherapy) received before study enrollment.
  • Unrelated patients.

You may not qualify if:

  • Cancer stage III/IV.
  • History of hematological cancer types or previous cancers, recurrent or relapse.
  • Diagnosis of inflammatory bowel diseases.
  • Pre-existing cardiovascular diseases or coronary artery diseases.
  • Confirmed treated or untreated autoimmune diseases.
  • Metabolic disorders, diabetes, or hypertension.
  • Neurological diseases.
  • Evidence of cardiac, renal, bone, or cerebral damage.
  • Presence of more than one type of malignancies.
  • Active infections or myositis.
  • Familial polyposis.
  • Alcohol or smoking habits.
  • Colon-affecting food allergies.
  • Body mass index (BMI) \>30.
  • Significant weight loss within the last 2 years.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Haykel Hospital

Tripoli, North Lebanon, 961, Lebanon

RECRUITING

Lebanese University

Tripoli, North Lebanon, 961, Lebanon

RECRUITING

MeSH Terms

Conditions

NeoplasmsThromboembolismCardiovascular DiseasesImmune System DiseasesColonic NeoplasmsBreast NeoplasmsProstatic NeoplasmsCarcinoma, HepatocellularLung NeoplasmsInflammationThrombosis

Interventions

palbociclibRivaroxaban

Condition Hierarchy (Ancestors)

Embolism and ThrombosisVascular DiseasesColorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesGenital Neoplasms, MaleUrogenital NeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeLiver NeoplasmsLiver DiseasesRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ThiophenesSulfur CompoundsOrganic ChemicalsMorpholinesOxazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Nehman Makdissy, Professor

    Lebanese University

    STUDY CHAIR

Central Study Contacts

Nehman Makdissy, Professor

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator, Professor

Study Record Dates

First Submitted

September 6, 2023

First Posted

October 4, 2023

Study Start

February 1, 2019

Primary Completion

December 1, 2024

Study Completion

December 1, 2024

Last Updated

October 6, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will not share

Locations