Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy

NCT ID: NCT04526886

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-15
• Study Completion Date: 2023-03-07

Brief 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 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.

Conditions

Colorectal Cancer; Gastric Cancer; Esophageal Cancer; Ampullary Cancer; Small Bowel Cancer; Appendix Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Arm

All patients in this single-arm study will be exposed to the experimental chemotherapy dose-adjustment algorithm.

Group Type: EXPERIMENTAL

Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy

Intervention Type: OTHER

Chemotherapy dose-adjustment algorithm for FOLFOX chemotherapy

Interventions

Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy

Chemotherapy dose-adjustment algorithm for FOLFOX chemotherapy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Gabriel A. Brooks

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gabriel A Brooks, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 31602321 (View on PubMed)

Wright 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.

Reference Type: DERIVED

PMID: 40779182 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

D20125

Identifier Type: -

Identifier Source: org_study_id