Clinical trial NCT04526886: Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy
Official title: A Pragmatic, Single-Arm Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Cancer
Gastric Cancer
Esophageal Cancer
Ampullary Cancer
Small Bowel Cancer
Appendix Cancer
Keywords: neutropenia
thrombocytopenia
FOLFOX
dose adjustment
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2020-08-26
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Unplanned chemotherapy treatment delay
timeFrame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
Secondary outcomes:
measure: Composite safety endpoint
timeFrame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
measure: Relative dose intensity of chemotherapy
timeFrame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
measure: Out of pocket costs associated with chemotherapy treatment visits
timeFrame: Single chemotherapy treatment visit on day 1 of cycle 3, 4, or 5 (cycle length is 14 days)
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Gabriel A Brooks, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.