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

NCT06307249 | Recruiting Phase 1 FDA Drug

• 1 other identifier: LU_HH_Cancer_Precision Therapy
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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).

  [Time Frame: up to 60 months]

• 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

  [ Time Frame: Once at the moment of the patient's enrollment in the study]

• 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.

  [ Time Frame: up to 60 months]

Secondary Outcomes (5)

• Survival Rates

  [ Time Frame: up to 60 months]

• Adverse Events

  [ Time Frame: up to 60 months]

• Assessment of Immune Checkpoint Expression (e.g., PD-1 and CTLA-4)

  [ Time Frame: up to 60 months]

• Measurement of Angiogenic Factors (e.g., VEGF)

  [ Time Frame: up to 60 months]

• Measurement of Tumor Proliferation Markers (e.g., Ki67, P16)

  [ Time Frame: up to 60 months].

Study Arms (4)

Carrier First-line Combined Therapy Group C-FL-CT

EXPERIMENTAL

This group of patients, who are carriers of the risk alleles, will receive combined therapy as the initial first-line treatment without prior chemotherapy.

Genetic: SNP; Drug: Palbociclib 125mg; Drug: Bevacizumab

Carrier Second-line Combined Therapy Group C-SL-CT

EXPERIMENTAL

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.

Genetic: SNP; Drug: Palbociclib 125mg; Drug: Bevacizumab

Non-carrier First-line Combined Therapy Group NC-FL-CT

EXPERIMENTAL

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.

Genetic: SNP; Drug: Palbociclib 125mg; Drug: Bevacizumab

Non-carrier Second-line Combined Therapy Group NC-SL-CT

EXPERIMENTAL

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.

Genetic: SNP; Drug: Palbociclib 125mg; Drug: Bevacizumab

Interventions

SNP GENETIC

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

Also known as: Risk Allele(s)

Carrier First-line Combined Therapy Group C-FL-CT; Carrier Second-line Combined Therapy Group C-SL-CT; Non-carrier First-line Combined Therapy Group NC-FL-CT; Non-carrier Second-line Combined Therapy Group NC-SL-CT

Palbociclib 125mg DRUG

Palbociclib 125mg/day/os over 21 days every 28 days

Also known as: anti-CDK4/6

Carrier First-line Combined Therapy Group C-FL-CT; Carrier Second-line Combined Therapy Group C-SL-CT; Non-carrier First-line Combined Therapy Group NC-FL-CT; Non-carrier Second-line Combined Therapy Group NC-SL-CT

Bevacizumab DRUG

10mg/kg every 21 days

Also known as: Anti-VEGF

Carrier First-line Combined Therapy Group C-FL-CT; Carrier Second-line Combined Therapy Group C-SL-CT; Non-carrier First-line Combined Therapy Group NC-FL-CT; Non-carrier Second-line Combined Therapy Group NC-SL-CT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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, 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lebanese University: lead
• Haykel Hospital: collaborator

Study Sites (2)

Haykel Hospital

Tripoli, North Lebanon, 961, Lebanon

RECRUITING

Lebanese University

Tripoli, North Lebanon, 961, Lebanon

RECRUITING

MeSH Terms

Conditions

Neoplasms; Colorectal Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Lung Neoplasms; Inflammation

Interventions

palbociclib; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nehman Makdissy, Professor

  Lebanese University

  STUDY CHAIR

Central Study Contacts

Nehman Makdissy, Professor

CONTACT

71210250; nehman.makdissy@ul.edu.lb

Study Design

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

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: March 12, 2024
• Study Start: February 15, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

LE (2)