Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer (FOXRegimen)

June 18, 2026 updated by: Gabriel A. Brooks, Dartmouth-Hitchcock Medical Center

Adaptive, Individualized Dose Escalation of Fluorouracil-Based Chemotherapy for Gastrointestinal Cancer: Pilot Study of the FOX Regimen

This is a single-arm clinical trial to evaluate the feasibility of a chemotherapy regimen using adaptive, individualized dose escalation of 5-FU chemotherapy for patients who have good tolerance of the initial dose. Study participants will also receive oxaliplatin chemotherapy together with 5-FU, at standard doses. The goal of the study is to examine the feasibility and effectiveness of this approach, using individualized dose escalation of 5-FU in patients who do not have serious side effects at lower doses.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Recruiting
        • Dartmouth-Hitchcock Medical Center
        • Contact:
        • Principal Investigator:
          • Gabriel A Brooks, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Diagnosis of metastatic or locally advanced/inoperable colorectal cancer or non-colorectal gastrointestinal cancer (including cancers of the stomach, esophagus, appendix, small bowel, and ampulla)
  • Clinically appropriate staging imaging of the chest, abdomen, and pelvis performed within 30 days prior to registration
  • ECOG Performance Status: 0-1

Exclusion Criteria:

  • Any prior receipt of oxaliplatin or fluoropyrimidine chemotherapy (other than radiation-sensitizing fluoropyrimidine chemotherapy)
  • Prior receipt of systemic chemotherapy in the 6 months prior to Day 1 of Cycle 1 of FOX (other than radiation-sensitizing chemotherapy)
  • Known mismatch repair deficiency or microsatellite instability-high disease
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency, as identified by clinically indicated screening
  • Any confirmed second malignancy that is likely to require systemic therapy during the course of the six-month study period, in the opinion of the enrolling investigator

  • Any of the following baseline laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 2,500/mm3
    • Platelet count < 100,000/mm3
    • Hemoglobin < 9 g/dL
    • Creatinine > 1.5 x ULN
    • Total bilirubin > 1.5 x ULN
    • AST/ALT > 5 x ULN
    • Patients who are unable to provide informed consent
    • Patients who are pregnant or breastfeeding
    • Patients who are incarcerated, homeless, or have active substance use disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Study Arm
All patients in this single-study arm will be exposed to the FOX regimen, an adaptively dose-escalated chemotherapy regimen. The FOX regimen is comprised of oxaliplatin 85 mg/m2 IV on Day 1; leucovorin calcium 350 mg IV on Day 1; and infusional 5-FU IV over 46 hours (Days 1 and 2) - starting at a dose of 2,400 mg/m2 and adaptively adjusted toward a maximum dose of 3,200 mg/m2 over Cycles 2-4 using a clinical algorithm.
Other: FOX dose-escalation algorithm
Chemotherapy dose-escalation algorithm based on the FOLFOX and FOLFOXIRI regimens

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of patients that receive dose intensified infusional 5-FU in Cycle 6 of the FOX regimen
Time Frame: Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
The proportion of patients who receive dose-intensified infusional 5-FU (dosed at greater than or equal to 2,800 mg/m2) in Cycle 6 of the FOX regimen.
Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Response rate to chemotherapy
Time Frame: Through 6 months from Cycle 1 Day 1 of FOX regimen
Response rate (stratified by colorectal cancer vs. gastroesophageal cancer) as defined using RECIST 1.1 imaging criteria
Through 6 months from Cycle 1 Day 1 of FOX regimen
Progression-free survival
Time Frame: Through 12 months from Cycle 1 Day 1 of FOX regimen
Progression-free survival (PFS, stratified by colorectal cancer vs. gastroesophageal cancer, determined by retrospective review of medical records)
Through 12 months from Cycle 1 Day 1 of FOX regimen
Dose intensity of 5-FU and oxaliplatin
Time Frame: Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
Dose intensity of 5-FU and oxaliplatin over Cycles 1-6. Dose intensity will be calculated separately for each component of the FOLFOX regimen (5-FU infusion and oxaliplatin).
Through day 1 of Cycle 6 of FOX regimen (cycle length is 14 days)
Mean plasma uracil concentration
Time Frame: Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)
Difference in mean plasma uracil concentration between patients who did and did not achieve sustained 5-FU dose escalation to ≥ 2,800 mg/m2 (primary endpoint)
Single treatment visit 0-30 days before Day 1 of Cycle 1 of FOX regimen, (cycle length is 14 days)
5-FU drug exposure
Time Frame: Single treatment visit on Day 3 of treament Cycle 5 or Cycle 6 of FOX regimen, (cycle length is 14 days)
5-FU drug exposure, measured as the area under the drug concentration curve (AUC). AUC will be calculated by multiplying the measured 5-FU concentration at steady state by the 5-FU infusion duration in hours.
Single treatment visit on Day 3 of treament Cycle 5 or Cycle 6 of FOX regimen, (cycle length is 14 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dartmouth-Hitchcock Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gabriel A Brooks, M.D., Dartmouth-Hitchcock Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 14, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 22, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY02001873
  • 22BRO873 (Other Identifier: Dartmouth Health)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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