Ampullary Cancer, Appendix Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer, Small Bowel Cancer
Conditions
Keywords
neutropenia, thrombocytopenia, FOLFOX, dose adjustment
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.
Interventions
OTHERAlgorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy
Chemotherapy dose-adjustment algorithm for FOLFOX chemotherapy
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unplanned Chemotherapy Treatment Delay | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Safety Endpoint | Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days) | 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) |
| Relative Dose Intensity of Chemotherapy | Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days) | 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). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the Dartmouth Cancer Center from the Lebanon, NH, St. Johnsbury, VT, and Nashua, NH, clinic sites between September 14, 2020 and December 14, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Evaluable Subjects All patients in this single-arm study will be exposed to the experimental chemotherapy dose-adjustment algorithm.
Algorithm for cytopenia-related delay and dose-reduction of mFOLFOX chemotherapy: Chemotherapy dose-adjustment algorithm for FOLFOX chemotherapy | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Evaluable Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 26 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 66 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment United States | 48 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 52 |
| other Total, other adverse events | 4 / 52 |
| serious Total, serious adverse events | 0 / 52 |
Outcome results
Primary
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.
Time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evaluable Participants | Unplanned Chemotherapy Treatment Delay | 16 Participants |
Secondary
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)
Time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evaluable Participants | Composite Safety Endpoint | 3 Participants |
Secondary
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).
Time frame: Through day 1 of cycle 6 of FOLFOX chemotherapy (cycle length is 14 days)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Evaluable Participants | Relative Dose Intensity of Chemotherapy | 5-FU infusion | 0.913 Percentage |
| Evaluable Participants | Relative Dose Intensity of Chemotherapy | Oxaliplatin | 0.850 Percentage |
| Evaluable Participants | Relative Dose Intensity of Chemotherapy | 5-FU bolus | 0.643 Percentage |