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Trial Title: Precision Therapy for Solid Tumors: Synergistic CDK4/6 Inhibition and Anti-VEGF Targeting LncRNA

NCT ID: NCT06307249

Condition: Cancer
Solid Tumor
Colorectal Cancer
Breast Cancer
Ovarian Cancer
Lung Cancer
Targeted Therapy
Chemotherapy
Immunotherapy
Precision Therapy

Conditions: Official terms:
Bevacizumab
Palbociclib

Conditions: Keywords:
LncRNA
Anti-VEGF
CDK4/6 inhibitor
Gene Polymorphism
Palbociclib
Bevacizumab
Inflammation
Immune Cells
Angiogenesis
Proliferative
Cancer

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Single (Participant)

Intervention:

Intervention type: Genetic
Intervention name: SNP
Description: Diagnostics of patients' carriers or not of the risk allele(s)
Arm group label: Carrier First-line Combined Therapy Group C-FL-CT
Arm group label: Carrier Second-line Combined Therapy Group C-SL-CT
Arm group label: Non-carrier First-line Combined Therapy Group NC-FL-CT
Arm group label: Non-carrier Second-line Combined Therapy Group NC-SL-CT

Other name: Risk Allele(s)

Intervention type: Drug
Intervention name: Palbociclib 125mg
Description: Palbociclib 125mg/day/os over 21 days every 28 days
Arm group label: Carrier First-line Combined Therapy Group C-FL-CT
Arm group label: Carrier Second-line Combined Therapy Group C-SL-CT
Arm group label: Non-carrier First-line Combined Therapy Group NC-FL-CT
Arm group label: Non-carrier Second-line Combined Therapy Group NC-SL-CT

Other name: anti-CDK4/6

Intervention type: Drug
Intervention name: Bevacizumab
Description: 10mg/kg every 21 days
Arm group label: Carrier First-line Combined Therapy Group C-FL-CT
Arm group label: Carrier Second-line Combined Therapy Group C-SL-CT
Arm group label: Non-carrier First-line Combined Therapy Group NC-FL-CT
Arm group label: Non-carrier Second-line Combined Therapy Group NC-SL-CT

Other name: Anti-VEGF

Summary: 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.

Detailed description: This innovative clinical trial applies a comprehensive strategy to study the complex interplay of biomarkers, immune responses, angiogenesis, and proliferation in solid tumor progression. This approach integrates the selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, such as Palbociclib, with the angiogenesis inhibitor, like Bevacizumab. This dual-targeted therapy holds promise for treating various solid tumors, including colorectal cancer, breast cancer, lung cancer, ovarian cancer, and others. A focal point of the study is the investigation of Long Non-Coding RNA (LncRNA) , chosen for its potential as a prognostic and predictive biomarker. LncRNA plays a multifaceted role in cellular processes, influencing cell cycle checkpoints, angiogenesis, and metastasis. Its aberrant expression across different cancers positions as a key subject of investigation, particularly considering its potential association with polymorphisms. Beyond its involvement in proliferation and angiogenesis. It also adds an additional layer of complexity, crucial for understanding patient outcomes. The investigation initiates with colorectal cancer and extends to other solid cancers, including lung, ovarian, and breast cancers. Patients are stratified into carriers or non-carriers of the risk allele, forming the foundation for precision-driven treatments. The study design comprises two distinct groups within the colorectal cancer cohort, Group 1 and Group 2, involving patients with and without the risk allele. These groups undergo combined therapy with a CDK4/6 inhibitor and anti-VEGF. Similarly, the distribution is maintained for patients with and without the risk allele in other solid tumors (lung, breast, ovarian, etc.), receiving the same combined therapy tailored to their molecular profiles whether taken as 1st line of treatment or 2nd line of treatment. Precise pre-treatment assessments establish baseline parameters, while post-treatment evaluations cover outcomes such as tumor progression, cancer regression, survival rates, and thromboembolic events. The interdependent relationship between proliferative tumor cells and angiogenesis, coupled with the potential impact of thromboembolism, is pivotal for cancer progression. Dysregulated cell cycle machinery, often involving overactive cyclin-dependent kinases (CDKs) like CDK4/6, drives uncontrolled proliferation, leading to a hypoxic microenvironment that triggers angiogenesis. Recognizing this symbiosis, the rationale for combining Palbociclib, a CDK4/6 inhibitor, with Bevacizumab, an anti-VEGF agent, becomes evident. While Palbociclib disrupts the cell cycle progression of proliferating tumor cells, hindering their uncontrolled growth, Bevacizumab concurrently targets the angiogenic process by inhibiting VEGF. This dual-targeted approach aims to comprehensively address both the proliferative, angiogenic, and thromboembolic facets of tumor biology, potentially leading to a more effective and synergistic anti-tumor response. Four groups will be considered: Carrier Groups: Group 1: "Carrier First-line Combined Therapy Group", C-FL-CT; Group 2: "Carrier Second-line Combined Therapy Group", C-SL-CT Non-carrier Groups: Group 3: "Non-carrier First-line Combined Therapy Group", NC-FL-CT; Group 4: "Non-carrier Second-line Combined Therapy Group", NC-SL-CT "Carrier"" denotes the patient who possesses the risk allele of the LncRNA CDKN2B-AS1. Group 1: This group of patients, who are carriers of the risk alleles, will receive combined therapy as the initial first-line treatment without prior chemotherapy. Group 2: This group of patients, who are carriers of the risk alleles, will receive combined therapy after having undergone prior chemotherapy, making it the second-line treatment. Group 3: This group of patients, who are non-carriers of the risk alleles, will receive combined therapy as the initial first-line treatment without prior chemotherapy. Group 4: This group of patients, who are non-carriers of the risk alleles, will receive combined therapy after having undergone prior chemotherapy, making it the second-line treatment. In summary, the study integrates precision medicine, biomarker-driven therapies, and a comprehensive understanding of the molecular basis of tumor progression, including thromboembolism. This approach offers a promising avenue for the development of personalized and effective treatments for various solid tumors, emphasizing not only efficacy and safety but also the overall effectiveness of the proposed therapeutic interventions.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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). - Cancer stage III/ IV with or without metastasis or lymph node dissemination at the time of enrollment. - Unrelated patients. Exclusion Criteria: - 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. - Body mass index (BMI) >30. - Significant weight loss within the last 2 years. - History of surgeries. - Pregnancy. - Related patients.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Haykel Hospital

Address:
City: Tripoli
Zip: 961
Country: Lebanon

Status: Recruiting

Contact:
Last name: David Wehbe, MD
Email: Wehbehdavid@hotmail.com

Contact backup:
Last name: Malak Naboulsi, PharmD
Email: malak.naboulsi@gmail.com

Facility:
Name: Lebanese University

Address:
City: Tripoli
Zip: 961
Country: Lebanon

Status: Recruiting

Contact:
Last name: Neham Makdissy, Professor

Phone: 71210250

Phone ext: +961
Email: nehman.makdissy@ul.edu.lb

Investigator:
Last name: Samar Hamoui, PhD
Email: Sub-Investigator

Investigator:
Last name: Fida Ayoubi, PhD
Email: Sub-Investigator

Investigator:
Last name: Nouha Ibrahim, PhD
Email: Sub-Investigator

Investigator:
Last name: Nadine Ghotme, PhD
Email: Sub-Investigator

Investigator:
Last name: Elisa Makdessi, PhD Student
Email: Sub-Investigator

Start date: February 15, 2023

Completion date: December 2027

Lead sponsor:
Agency: Lebanese University
Agency class: Other

Collaborator:
Agency: Haykel Hospital
Agency class: Other

Source: Lebanese University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06307249

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