Solid tumors pose significant challenges in current therapeutic approaches. Targeted therapy has emerged as a promising avenue, aiming to enhance treatment efficacy while minimizing adverse effects. This clinical trial focuses on an innovative combination of two targeted inhibitors, Palbociclib and Bevacizumab, for their potential synergistic effects in addressing these challenging malignancies. Moreover, this study incorporates a molecular approach by considering Long Non-Coding RNAs (LncRNAs) as biomarkers. Initiating with a focus on colorectal cancer, the study aims to expand its scope to other solid tumors, including lung, breast, ovarian and other cancers. Palbociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, disrupts the cell cycle progression, particularly in cancer cells with specific molecular characteristics. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, targets angiogenesis-a critical process for tumor growth and metastasis. The rationale behind combining these agents lies in their complementary mechanisms of action, potentially leading to enhanced antitumor effects. LncRNAs have shown promise in predicting treatment response and prognosis in various cancers, providing an additional layer of precision to the treatment strategy. By elucidating the molecular basis through LncRNA analysis, the trial aims to tailor the treatment to the specific molecular profile of each patient, ultimately striving for better outcomes and improved survival rates. This novel combination therapy, coupled with a personalized biomarker-driven approach, represents a cutting-edge strategy in the pursuit of more effective and individualized treatment for solid tumors.
Individuals of white ethnicity.
Age between > 18
Both males and females.
Diagnosis of selected cancer type (e.g., colorectal cancer, lung cancer, genitourinary cancers, breast cancer).
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.
Parallel
SNP
GeneticDiagnostics of patients' carriers or not of the risk allele(s)
Palbociclib 125mg
DrugPalbociclib 125mg/day/os over 21 days every 28 days
Bevacizumab
Drug10mg/kg every 21 days
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). 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 based on RECIST guidelines, considering an increase in tumor size or the appearance of new lesions according to imaging assessments (e.g., CT, MRI, or PET scans) and clinical evaluations (including tumor markers and histopathological analysis).
Identification of Potential Biomarkers
Finding and characterizing new biomarkers linked to thromboembolism and the advancement of cancer is the aim of this result. The evaluation will pay particular attention to Long Non-Coding RNAs (LncRNAs). At the time of study enrollment, biological samples (such as blood or tissue) from enrolled patients will be collected as part of the identification procedure. With Ct (Cycle threshold) serving as the standard unit of measurement for all genes, the evaluation will employ quantitative PCR (qPCR) to study and assess the expression and polymorphisms of the investigated genes. This thorough evaluation seeks to further our knowledge of the molecular markers and the course of cancer, shedding light on new pathways for diagnosis and treatment that might lead to better patient outcomes
Evaluation of Treatment Response to Palbociclib and Bevacizumab Combination Therapy
This main outcome evaluates the extent to which patients responding to combination therapy are managing both angiogenesis and the cancer cell cycle progression. The percentage change in tumor size, a measure of therapy efficacy, will be calculated using the RECIST criteria in the evaluation.
Survival Rates
Analysis of overall survival and progression-free survival rates among groups
Adverse Events
Monitoring and reporting of adverse events related to the Palbociclib and Bevacizumab treatment regimen.
Assessment of Immune Checkpoint Expression (e.g., PD-1 and CTLA-4)
The expression of immunological checkpoint molecules, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) is the main emphasis of this result. The goal is to comprehend how immunological checkpoints control the immune response. PCR or flow cytometry will be used to determine immunological checkpoint expression as part of the evaluation. The percentage of change in PD-1 and CTLA-4 expression levels throughout a 60-month period in comparison to their levels at the diagnostic time will be used to measure the results. Over the course of the study, a thorough knowledge of the immune checkpoint dynamics and their influence on the immune response is made possible by the consistent evaluation that is ensured by the use of a standardized common unit of measure.
Measurement of Angiogenic Factors (e.g., VEGF)
This study aims to evaluate the angiogenic factor Vascular Endothelial Growth Factor (VEGF) post-treatment. VEGF plays a crucial role in regulating angiogenesis and is linked to tumor vascularization. The serum concentrations of VEGF-A/C will be measured by ELISA, providing valuable insights into the angiogenic processes linked to the treatment outcomes.
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Lebanese University
Lead sponsor
Haykel Hospital
Collaborator
