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