Phase I Trial of 5-Fluorouracil (5FU) -Based Therapy in Combination With Hydroxytyrosol (HT) in Patients With Advanced or Metastatic Colorectal Cancer

NCT06833866 | Recruiting Phase 1 FDA Drug

• 1 other identifier: Pro00038031
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Advanced or Metastatic CRC

Keywords

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Through study completion, up to 2 years

Secondary Outcomes (2)

• Progression-Free Survival (PFS) at 6 and 12 Months

  6 and 12 months post study drug initiation

• Objective Response Rate (ORR) According to RECIST v1.1

  Through study completion, up to 2 years

Other Outcomes (4)

• Changes in Health-Related Quality of Life (QoL)

  Baseline, 6 months, and 12 months

• Immune T-Cell Profiling in Blood and Tissue Samples

  Baseline, 2 weeks after HT initiation, and up to 100 weeks (from baseline to disease progression)

• Assessment of Tissue Immune Cells

  Baseline and post-treatment biopsy (up to 100 weeks, at disease progression or prior to surgery, if applicable)

Study Arms (1)

Hydroxytyrosol (HT) in combination with Folfiri/Folfox

EXPERIMENTAL

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

Drug: Hydroxytyrosol

Interventions

Hydroxytyrosol DRUG

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

Also known as: Folfiri/Folfox

Hydroxytyrosol (HT) in combination with Folfiri/Folfox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Life expectancy ≥6 months.
• Females of childbearing potential must agree to use birth control during the study and for 30 days after your last dose of HT, at least 9 months after your last dose of oxaliplatin, at least 3 months after your last dose of 5-FU, and at least 6 months after your last dose of irinotecan.
• Male who are sexually active and their partner can become pregnant, must agree to use birth control during the study and for 30 days after their last dose of HT, at least 6 months after their last dose of oxaliplatin, at least 3 months after his last dose of 5-FU, and at least 3 months after his last dose of irinotecan.

You may not qualify if:

• Hematology laboratory values of:
• 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)
• Hepatic laboratory values of aspartate transaminase or alanine aminotransferase:
• \>5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or
• \>2.5 × ULN if no liver metastases are present.
• Serum albumin \<2.8 g/dL.
• Total bilirubin \>1.5 × ULN or \>1.5 mg/dL.
• Prothrombin time (PT) or international normalized ratio (INR) \>1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.
• Estimated glomerular filtration rate \<50 mL/min.
• Positive pregnancy test, pregnant, or breastfeeding (female patients only).
• Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study.
• Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including, but not limited to:
• Arrhythmia

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist.

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

3,4-dihydroxyphenylethanol; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Abdullah Esmail, MD

  Houston Methodist Neal Cancer Center

  STUDY DIRECTOR

Central Study Contacts

Jennifer Garrett M Clinical Trials Manager, MSN

CONTACT

281-222-9983; jmgarrett@houstonmethodist.org

Kimberly Vu Clinical Research Nurse, BSN

CONTACT

936-270-2037; kvu2@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: February 19, 2025
• Study Start: December 4, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)