This is a phase I study investigating the safety and antitumor activity of 5FU-based therapy (FOLFIRI/FOLFOX + Biologics) in combination with Hydroxytyrosol (HT) as a treatment for patients with advanced or metastatic colorectal cancer.
Patients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression.
The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity
Male or female ≥18 years of age.
Histopathologically or cytologically confirmed advanced or metastatic CRC.
Patient who is eligible for first-line therapy for advanced or metastatic CRC, such as 5FU-based therapy.
Measurable disease per the RECIST v1.1.
WBC of <3000 and absolute neutrophil count ≤1500 cells/mm3 with the Fy null phenotype.
Platelets ≤100,000 cells/mm3
Hemoglobin ≤9 g/dL (Fe infusion is allowed to correct anemia in iron deficient anemia patients, per standard-of-care)
>5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or
Single group
Hydroxytyrosol
DrugPatients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression. The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity
Safety, Toxicity, and Pharmacokinetic/Pharmacodynamic (PK/PD) Profile of HT in Combination with FOLFIRI/FOLFOX + Biologics
Evaluation of safety profile, toxicity, and PK/PD parameters in patients receiving HT with 5FU-based therapy according to NCI CTCAE v5.0.
Progression-Free Survival (PFS) at 6 and 12 Months
Measurement of PFS at 6 months and 12 months, based on tumor assessment using RECIST v1.1 criteria.
Objective Response Rate (ORR) According to RECIST v1.1
Proportion of patients achieving partial response (PR) or complete response (CR) as per RECIST v1.1.
Changes in Health-Related Quality of Life (QoL)
Assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Immune T-Cell Profiling in Blood and Tissue Samples
Analysis of T-cell clusters in pretreatment tissue and blood and on-treatment blood (after 2 weeks on HT alone). Evaluation of CD4+, CD8+ T cells, and CD8+ T-cell:Treg ratio using multiplexed IF \& single-cell RNA sequencing (scRNA-seq).
Assessment of Tissue Immune Cells
Quantification of tissue immune cells using flow cytometry.
Analysis of Regulatory Proteins and Plasma Cytokines
Evaluation of regulatory proteins and plasma cytokines using a multiplexed protein array.
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