Advanced or Metastatic CRCPhase 1NCT06833866
Phase I Trial of 5-Fluorouracil (5FU) -Based Therapy in Combination With Hydroxytyrosol (HT) in Patients With Advanced or Metastatic Colorectal Cancer
A Phase 1 study testing Hydroxytyrosol in people with Advanced or Metastatic CRC, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic CRC
- What is being tested?
- Hydroxytyrosol
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Dec 2024to 1 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject will be eligible for inclusion in this study only if all the following criteria are met:
- 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.
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- 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.
- -
Who cannot join
- Subjects must meet all the inclusion criteria listed above in Section 10.1 and none of the following exclusion criteria:
- 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:
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- >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
- Bradycardia
- Tachycardia
- Symptomatic valvular disease
- Symptomatic congestive heart failure classified by the New York Heart Association as Class III or IV
- Unstable angina pectoris.
- Myocardial infarction within the past 6 months.
- Active bleeding diathesis (platelets less than 100,000 or active bleeding)
- Current complaints of persistent constipation or history of chronic constipation, bowel obstruction, or fecaloma within the past 6 months.
- Receiving chronic treatment with corticosteroids ≥5 mg of prednisone per day (or equivalent) or other immunosuppressive agents
- Known history and/or uncontrolled hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV)-1 or HIV-2.
- History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption.
- Receipt of live, attenuated vaccine (e.g., intranasal influenza, measles, mumps, rubella, varicella) or close contact with someone who has received a live, attenuated vaccine within the past 1 month. Note: Influenza vaccine will be allowed if administered >21 days.
- Receipt of any investigational agent or study treatment within the past 30 days.
- Receipt of any protein or antibody-based therapeutic agents (e.g., growth hormones or monoclonal antibodies) within the past 3 months.
- Patients must be able to swallow oral capsules.
- Participants with metastatic CRC and microsatellite instability-high or deficient mismatch repair tumors.
- surgical Surgery, within 12-months or less.
- For patients to be treated with bevacizumab: history of gastrointestinal fistula or perforation, major surgery within 28 days of study treatment initiation, recent hemorrhage, arterial thromboembolic events or deep venous thrombosis within 6 months, uncontrolled hypertension (i.e., BP > 150/90 mm Hg), proteinuria, and hemoptysis.
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Houston Methodist.
Houston, Texas, 77030
Jennifer Garrett M Clinical Trials Manager, MSN, 281-222-9983, jmgarrett@houstonmethodist.org
aesmail@houstonmethodist.org
About this study
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
- Being tested
- Hydroxytyrosol
- Keywords
- Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxytyrosolDrug
Also called Folfiri/Folfox
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Hydroxytyrosol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, up to 2 years
Secondary outcomes (2)
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.
Measured: 6 and 12 months post study drug initiation
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.
Measured: Through study completion, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2025
- Study start4 Dec 2024
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic CRCStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maen Abdelrahim, MD, PhD, Pharm.B, The Methodist Hospital Research Institute
- Investigators
- Abdullah Esmail, MD, Study director, Houston Methodist Neal Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06833866
- Sponsor's protocol ID
- Pro00038031
- Status last verified
- Oct 2026
- First submitted
- 15 Jan 2025
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of 5-Fluorouracil (5FU) -Based Therapy in Combination With Hydroxytyrosol (HT) in Patients With Advanced or Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06833866
- Acronym / sponsor ID
- Pro00038031
- Conditions
- Advanced or Metastatic CRC
- Keywords
- Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- 4 Dec 2024 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 19 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hydroxytyrosol (HT) in combination with Folfiri/Folfox | Experimental | Drug: HydroxytyrosolPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- A subject will be eligible for inclusion in this study only if all the following criteria are met:
- 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.
Key exclusion criteria (35 listed)
- Subjects must meet all the inclusion criteria listed above in Section 10.1 and none of the following exclusion criteria:
- Hematology laboratory values of:
- Hepatic laboratory values of aspartate transaminase or alanine aminotransferase:
- Serum albumin <2.8 g/dL.
- Total bilirubin >1.5 × ULN or >1.5 mg/dL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxytyrosolAlso: Folfiri/FolfoxPatients 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 (HT) in combination with Folfiri/Folfox |
Primary outcome
Safety, Toxicity, and Pharmacokinetic/Pharmacodynamic (PK/PD) Profile of HT in Combination with FOLFIRI/FOLFOX + Biologics
Time frame: Through study completion, up to 2 years
Evaluation of safety profile, toxicity, and PK/PD parameters in patients receiving HT with 5FU-based therapy according to NCI CTCAE v5.0.
2 secondary outcomes
Progression-Free Survival (PFS) at 6 and 12 Months
Time frame: 6 and 12 months post study drug initiation
Objective Response Rate (ORR) According to RECIST v1.1
Time frame: Through study completion, up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Abdullah Esmail, MD study director
Houston Methodist Neal Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hydroxytyrosol in people with Advanced or Metastatic CRC, run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Garrett M Clinical Trials Manager, MSN (281-222-9983, jmgarrett@houstonmethodist.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, Toxicity, and Pharmacokinetic/Pharmacodynamic (PK/PD) Profile of HT in Combination with FOLFIRI/FOLFOX + Biologics (time frame: Through study completion, up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.