Colorectal CancerNCT04526886
Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy
A study testing Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy in people with Colorectal Cancer and Gastric Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
The study is testing an intervention of an investigator-developed chemotherapy dose adjustment algorithm. The primary objective of this study is to evaluate the effectiveness of the chemotherapy dose adjustment algorithm for reducing unplanned delays in patients receiving FOLFOX (5-fluorouracil, leucovorin, and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Gastric Cancer, Esophageal Cancer
- What is being tested?
- Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2020to 7 Mar 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age greater than 18
- Diagnosis of adenocarcinoma of the gastrointestinal tract (to include cancers of the colorectum, stomach, esophagus, appendix, and small bowel)
- The treating oncologist's recommendation must be for six or more cycles of standard-dose mFOLFOX chemotherapy (with or without concurrent bevacizumab, cetuximab, panitumumab, or trastuzumab). Intent of treatment may be either curative or palliative in nature.
- Completion of day 1 of cycle 1 of standard-of-care FOLFOX chemotherapy
Who cannot join
- Prior receipt of systemic chemotherapy in the 12 months prior to day 1 of cycle 1 of mFOLFOX (other than radiation-sensitizing chemotherapy)
- History of baseline neutropenia; defined as neutrophil count <1500 in the 30 days preceding planned day 1 of cycle 1 of mFOLFOX
- History of baseline thrombocytopenia; defined as platelet count <100,000) in the 30 days preceding planned day 1 of cycle 1 of mFOLFOX
- Patients with a history of an uncorrected bleeding condition that would preclude safe use of the dose adjustment algorithm, in the judgement of the enrolling investigator
- Patients who have started a new prescription anticoagulant (e.g. warfarin, heparin derivatives, or direct oral anticoagulants) in the 14 days preceding day 1 of cycle 1 of mFOLFOX
- Patients who are unable to provide informed consent
- Pregnant women
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: A Pragmatic, Single-Arm Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy
The study is testing an intervention of an investigator-developed chemotherapy dose adjustment algorithm. The primary objective of this study is to evaluate the effectiveness of the chemotherapy dose adjustment algorithm for reducing unplanned delays in patients receiving FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin)-type chemotherapy, while maintaining acceptable chemotherapy dose-intensity.
Read the detailed description
The study intervention will involve implementation of a clinical algorithm to guide chemotherapy dose reductions and treatment delays in patients with neutropenia and/or thrombocytopenia during treatment with FOLFOX-type regimens. The clinical algorithm was developed by the principal investigator, and the algorithm has been iteratively revised over time based on experiences from use in routine care.
Features of the dose adjustment algorithm that differ from criteria used in clinical trial protocols and routine care include:
- At presentation for cycle 2 and 3 - the algorithm employs proactive chemotherapy dose reductions, without treatment delay, in patients with mild cytopenias (absolute neutrophil count [ANC] 1000-1499/mm3 and/or platelet count 75,000-99,000/mm3). In usual care, mild cytopenias during early treatment cycles do not trigger a chemotherapy dose reduction, but these early cytopenia events often lead to more severe cytopenias and subsequent delays in later treatment cycles.
- At any cycle - the algorithm employs chemotherapy dose reductions without treatment delay in patients with moderate cytopenias (ANC 750-999/mm3 and/or platelet count 50,000-74,000/mm3). In usual care, moderate cytopenias trigger both a chemotherapy treatment delay AND a subsequent dose reduction, whereas the study algorithm will introduce a dose reduction without a treatment delay.
Decisions about dose modifications and delays for reasons other than neutropenia and/or thrombocytopenia will be made at the discretion of the treating clinician, as per standard-of-care treatment.
- Conditions
- Colorectal Cancer, Gastric Cancer, Esophageal Cancer, Ampullary Cancer, Small Bowel Cancer, Appendix Cancer
- Being tested
- Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy
- Keywords
- neutropenia, thrombocytopenia, FOLFOX, dose adjustment
- Medical subject headings
- Colorectal Neoplasms, Stomach Neoplasms, Esophageal Neoplasms, Appendiceal Neoplasms, Neutropenia, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapyOther
Chemotherapy dose-adjustment algorithm for FOLFOX chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Study Arm | Experimental | All patients in this single-arm study will be exposed to the experimental chemotherapy dose-adjustment algorithm. Receives: Other: Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unplanned Chemotherapy Treatment Delay
Number of patients with any interruption of chemotherapy leading to a cycle length of >18 days that is not anticipated as of day 3 of the preceding treatment cycle.
Measured: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Secondary outcomes (2)
Composite Safety Endpoint
Number of patients meeting the composite endpoint of 1) febrile neutropenia (grade 3 or 4), 2) major bleeding with concurrent grade 3 thrombocytopenia (platelet count <50,000/mm3), 3) CTCAE grade 4 neutropenia (ANC <500/mm3), and/or 4) CTCAE grade 4 thrombocytopenia (platelet count <25,000/mm3)
Measured: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Relative Dose Intensity of Chemotherapy
Relative dose intensity (RDI) of chemotherapy. RDI is defined as (planned cumulative dose/cumulative administered dose)*(actual duration/planned duration). RDI will be calculated separately for each component of the FOLFOX regimen (5-FU bolus, 5-FU infusion, oxaliplatin).
Measured: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2020
- Study start15 Oct 2020
- Primary completion7 Mar 2023
- Study completion7 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gabriel A. Brooks, Dartmouth-Hitchcock Medical Center
- Investigators
- Gabriel A Brooks, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526886
- Sponsor's protocol ID
- D20125
- Status last verified
- Sep 2025
- First submitted
- 20 Aug 2020
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kogan LG, Davis SL, Brooks GA. Treatment delays during FOLFOX chemotherapy in patients with colorectal cancer: a multicenter retrospective analysis. J Gastrointest Oncol. 2019 Oct;10(5):841-846. doi: 10.21037/jgo.2019.07.03.
PubMed 31602321Wright HN, Tosteson TD, Hourdequin KC, Ripple GH, Fuld AD, Dragnev KH, Amin M, Muralikrishnan S, McGrath EB, Stannard MG, Schofield LL, Lord-Halvorson S, Tosteson ANA, Brooks GA. A pragmatic, single-arm clinical trial of a dose modification algorithm for preventing cytopenia-related delays during FOLFOX chemotherapy. Support Care Cancer. 2025 Aug 8;33(9):769. doi: 10.1007/s00520-025-09784-0.
PubMed 40779182
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic, Single-Arm Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy
- ClinicalTrials.gov ID
- NCT04526886
- Acronym / sponsor ID
- D20125
- Conditions
- Colorectal Cancer, Gastric Cancer, Esophageal Cancer, Ampullary Cancer, Small Bowel Cancer, Appendix Cancer
- Keywords
- neutropenia, thrombocytopenia, FOLFOX, dose adjustment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 7 Mar 2023 (actual)
- Study completion
- 7 Mar 2023 (actual)
- First posted
- 26 Aug 2020 (actual)
- Results
- Posted 6 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is testing an intervention of an investigator-developed chemotherapy dose adjustment algorithm. The primary objective of this study is to evaluate the effectiveness of the chemotherapy dose adjustment algorithm for reducing unplanned delays in patients receiving FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin)-type chemotherapy, while maintaining acceptable chemotherapy dose-intensity.
Detailed description
The study intervention will involve implementation of a clinical algorithm to guide chemotherapy dose reductions and treatment delays in patients with neutropenia and/or thrombocytopenia during treatment with FOLFOX-type regimens. The clinical algorithm was developed by the principal investigator, and the algorithm has been iteratively revised over time based on experiences from use in routine care.
Features of the dose adjustment algorithm that differ from criteria used in clinical trial protocols and routine care include:
- At presentation for cycle 2 and 3 - the algorithm employs proactive chemotherapy dose reductions, without treatment delay, in patients with mild cytopenias (absolute neutrophil count [ANC] 1000-1499/mm3 and/or platelet count 75,000-99,000/mm3). In usual care, mild cytopenias during early treatment cycles do not trigger a chemotherapy dose reduction, but these early cytopenia events often lead to more severe cytopenias and subsequent delays in later treatment cycles.
- At any cycle - the algorithm employs chemotherapy dose reductions without treatment delay in patients with moderate cytopenias (ANC 750-999/mm3 and/or platelet count 50,000-74,000/mm3). In usual care, moderate cytopenias trigger both a chemotherapy treatment delay AND a subsequent dose reduction, whereas the study algorithm will introduce a dose reduction without a treatment delay.
Decisions about dose modifications and delays for reasons other than neutropenia and/or thrombocytopenia will be made at the discretion of the treating clinician, as per standard-of-care treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Arm | Experimental | Other: Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapyAll patients in this single-arm study will be exposed to the experimental chemotherapy dose-adjustment algorithm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age greater than 18
- Diagnosis of adenocarcinoma of the gastrointestinal tract (to include cancers of the colorectum, stomach, esophagus, appendix, and small bowel)
- The treating oncologist's recommendation must be for six or more cycles of standard-dose mFOLFOX chemotherapy (with or without concurrent bevacizumab, cetuximab, panitumumab, or trastuzumab). Intent of treatment may be either curative or palliative in nature.
- Completion of day 1 of cycle 1 of standard-of-care FOLFOX chemotherapy
Key exclusion criteria (7 listed)
- Prior receipt of systemic chemotherapy in the 12 months prior to day 1 of cycle 1 of mFOLFOX (other than radiation-sensitizing chemotherapy)
- History of baseline neutropenia; defined as neutrophil count <1500 in the 30 days preceding planned day 1 of cycle 1 of mFOLFOX
- History of baseline thrombocytopenia; defined as platelet count <100,000) in the 30 days preceding planned day 1 of cycle 1 of mFOLFOX
- Patients with a history of an uncorrected bleeding condition that would preclude safe use of the dose adjustment algorithm, in the judgement of the enrolling investigator
- Patients who have started a new prescription anticoagulant (e.g. warfarin, heparin derivatives, or direct oral anticoagulants) in the 14 days preceding day 1 of cycle 1 of mFOLFOX
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 |
|---|---|---|
| Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapyChemotherapy dose-adjustment algorithm for FOLFOX chemotherapy | Other | Study Arm |
Primary outcome
Unplanned Chemotherapy Treatment Delay
Time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Number of patients with any interruption of chemotherapy leading to a cycle length of >18 days that is not anticipated as of day 3 of the preceding treatment cycle.
2 secondary outcomes
Composite Safety Endpoint
Time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Relative Dose Intensity of Chemotherapy
Time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31602321Kogan LG, Davis SL, Brooks GA. Treatment delays during FOLFOX chemotherapy in patients with colorectal cancer: a multicenter retrospective analysis. J Gastrointest Oncol. 2019 Oct;10(5):841-846. doi: 10.21037/jgo.2019.07.03.
- Derived from this study: PubMed 40779182Wright HN, Tosteson TD, Hourdequin KC, Ripple GH, Fuld AD, Dragnev KH, Amin M, Muralikrishnan S, McGrath EB, Stannard MG, Schofield LL, Lord-Halvorson S, Tosteson ANA, Brooks GA. A pragmatic, single-arm clinical trial of a dose modification algorithm for preventing cytopenia-related delays during FOLFOX chemotherapy. Support Care Cancer. 2025 Aug 8;33(9):769. doi: 10.1007/s00520-025-09784-0.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Gabriel A Brooks, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy in people with Colorectal Cancer and Gastric Cancer, run by Dartmouth-Hitchcock Medical Center 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 4 inclusion and 7 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: finished, as of the sponsor's last update on 6 Oct 2025. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unplanned Chemotherapy Treatment Delay (time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04526886, which also lists 2 linked publications.
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 6 Oct 2025; AzTrials last refreshed its copy on 1 Nov 2026.