Summary

This clinical trial is being done to learn whether using the proactive, graduated dose modification algorithm for leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) (PAGODA) algorithm to guide chemotherapy dosing for the FOLFOX regimen works to reduce unplanned treatment delays for patients with digestive system cancers compared to usual care. During standard of care treatment, chemotherapy dose changes or treatment delays are typically determined by the treating physician based on factors such as a patient’s height, weight, and blood test results obtained before each treatment cycle. If certain blood counts are too low, the next cycle of chemotherapy may be delayed or adjusted. The PAGODA algorithm is a step-by-step decision-making tool designed to help health care providers determine whether chemotherapy doses should be adjusted or delayed in patients with low neutrophil or platelet counts. Researchers will compare treatment delays, dose changes, and safety outcomes between patients managed using the PAGODA algorithm and patients receiving usual care.

Objectives

PRIMARY OBJECTIVE:
I. To compare the proportion of chemotherapy cycles with unplanned delays in patients receiving FOLFOX chemotherapy under standardized usual care (control) versus (vs) according to the PAGODA dose modification algorithm (intervention).

SECONDARY OBJECTIVES:
I. To compare the mean number of health care contact days (time toxicity) for patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms.
II. To compare the incidence of moderate-to-severe neutropenia (absolute neutrophil count less than 1000/mm^3) in patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms.
III. To compare the relative dose-intensity of bolus 5-FU, oxaliplatin, and infusional 5-FU in patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms, both overall and among the subgroup of participants treated with curative intent.

EXPLORATORY OBJECTIVES:
I. To compare the mean number of cycles per patient with granulocyte colony stimulating factor (GCSF) support in patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms.
II. To compare overall survival after 2-year follow-up in patients receiving FOLFOX chemotherapy according to assignment to the control vs intervention arms.
IV. To compare the proportion of chemotherapy cycles with cytopenia-related unplanned delays according to assignment to the control vs intervention arms.
V. To evaluate the acceptability of the PAGODA dose modification algorithm from the perspective of oncologists and advanced practice providers.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive chemotherapy delays and dose modifications at the discretion of the treating clinician during cycles 2-7 of standard of care (SOC) FOLFOX chemotherapy on study.

ARM B: Patients receive chemotherapy delays and dose modifications based on PAGODA algorithm followed by treating clinician decision during cycles 2-7 of SOC FOLFOX chemotherapy on study.

After completion of study intervention, patients are followed up at 30 and 120 days and then every 12 months for 2 years following registration.

Eligibility

1. REGISTRATION ELIGIBILITY CRITERIA (STEP 1):
2. Histologic confirmation of invasive cancer that is confirmed or suspected to arise from the gastrointestinal (GI) tract
3. Any stage for which FOLFOX-based chemotherapy is a clinically-indicated, standard-of-care treatment (adjuvant, neoadjuvant, or first-line chemotherapy)
4. Eligible primary tumor sites include the esophagus, gastroesophageal junction, stomach, small intestine, ampulla of Vater, appendix, colon and rectum, as well as cancers of unknown primary with suspected GI origin
5. Prior systemic therapy for GI cancer (other than cycle 1 of FOLFOX-based chemotherapy) is not allowed. Prior radiation-sensitizing chemotherapy is permitted
6. The planned duration of FOLFOX-based chemotherapy must be at least four cycles (1 cycle = 14 days)
7. Cycle 1, day 1 of FOLFOX-based chemotherapy must be completed 1 to 8 days prior to registration
8. Cycle 1, day 1 of FOLFOX-based chemotherapy must include minimum ordered doses of oxaliplatin (= 65 mg/m^2) and infusional 5-FU (2400 mg/m^2/46 hours). Use of the 5-FU bolus is at the discretion of the treating physician
9. Concomitant monoclonal antibodies are permitted during FOLFOX-based chemotherapy (e.g. anti-VEGF, anti-EGFRs, anti-PD1/PDL1, and anti-HER2)
10. Patients receiving concomitant therapy with irinotecan or docetaxel are not eligible
11. Patients who require primary prophylactic white blood cell growth factor with cycle 1 of FOLFOX chemotherapy due to high risk for fever and neutropenia are not eligible
12. Patients with history of hypersensitivity reaction to oxaliplatin or other platinum-based drugs, to fluorouracil, or to leucovorin, and the excipients in their formulations are not eligible
13. Age = 18 years
14. Eastern Cooperative Oncology Group (ECOG) performance status = 2
15. Absolute neutrophil count (ANC) = 1,000/mm^3
16. Platelet count = 100,000/mm^3
17. Total bilirubin = 3 x upper limit of normal (ULN)
18. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = 5 x upper limit of normal (ULN)
19. Calculated (calc.) creatinine clearance = 30 mL/min
20. Not pregnant and not nursing, because this study involves agents that have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done = 30 days prior to registration is required
21. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
22. Patients with known HIV infection are eligible if receiving effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration
23. Patients with known chronic hepatitis B virus (HBV) infection are eligible if HBV deoxyribonucleic acid (DNA) is undetectable when measured within 6 months prior to registration
24. Patients with a known history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) is undetectable when measured at least 12 weeks after completion of antiviral therapy
25. Patients with a known history or current symptoms of cardiac disease are eligible if the New York Heart Association Functional Classification is class I or II (heart failure with no more than slight limitation of physical activity)
26. Patients with a known history of congenital long QT syndrome are ineligible
27. Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency are ineligible
28. NON-PATIENT (ONCOLOGY PHYSICIAN OR ONCOLOGY ADVANCED PRACTICE PROVIDER) ELIGIBILITY:
29. The non-patient provider participant is a medical oncologist or oncology advanced practice provider with responsibility for signing and making necessary modifications to chemotherapy orders for a subject assigned to the intervention arm (Arm B). Non-patient participants may not be enrolled more than once over the course of the study
30. The non-patient participant must be proficient in the English language
31. The non-patient participant must be age 21 years or older

Treatment Sites in Georgia