Studying the PAGODA Algorithm for Chemotherapy Dose Changes to Prevent Unplanned Treatment Delays

Official title

PAGODA: Randomized Trial of a Proactive Graduated Dose Modification Algorithm for FOLFOX Chemotherapy to Prevent Unplanned Delays

Overview

This study seeks to learn whether using the PAGODA algorithm to guide chemotherapy dosing will lower the chance of unplanned delays during chemotherapy for cancer in the gastrointestinal system compared to usual care.

Detailed description

The primary and secondary objectives of the study:

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 moderate-to-severe neutropenia (absolute neutrophil count less than 1000/mm3 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.

OUTLINE: This is an interventional study. 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 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.

Interventions

• Other PAGODA algorithm
  use PAGODA algorithm to determine chemotherapy delays and dose modifications
• Drug Oxaliplatin
  Given IV
• Drug Folinic Acid
  Given IV
• Drug Fluorouracil
  Given IV

Primary outcome measures

• Incidence of unplanned chemotherapy delays [Time frame: From cycle 2 to 7 (Undelayed cycle length= 14 days)]

Secondary outcome measures (3)

• Time toxicity [Time frame: From registration to 120 days after registration.]
• Moderate-to-severe neutropenia [Time frame: From the start of cycle 2 to 30 days after start of cycle 7 (undelayed cycle length= 14 days)]
• Chemotherapy relative dose intensity [Time frame: Time Frame: From the start of cycle 1 to day 14 of cycle 6 (undelayed cycle length= 14 days).]

Eligibility criteria

Inclusion criteria

• \* REGISTRATION ELIGIBILITY CRITERIA (STEP 1)

• Histologic confirmation of invasive cancer that is confirmed or suspected to arise from the gastrointestinal (GI) tract
• Any stage for which FOLFOX-based chemotherapy is a clinically-indicated, standard-of-care treatment (adjuvant, neoadjuvant, or first-line chemotherapy)
• Eligible primary tumor sites include the esophagus, gastroesophageal junction, stomach, small intestine, ampulla of Vater, appendix, colon, rectum, and cancers of unknown primary with suspected GI origin
• Prior systemic therapy for GI cancer (other than cycle 1 of FOLFOX-based chemotherapy) is not allowed. Prior radiation-sensitizing chemotherapy is permitted
• The planned duration of FOLFOX-based chemotherapy must be at least four cycles (1 cycle = 14 days)
• Cycle 1, day 1 of FOLFOX-based chemotherapy must be completed 1 to 8 days prior to registration
• 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
• 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
• 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
• Age ≥ 18 years
• ECOG performance status ≤ 2
• Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Total bilirubin ≤ 3 x upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 5 x upper limit of normal (ULN)
• Calc. creatinine clearance ≥ 30 mL/min
• 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
• Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression
• Patients with known HIV infection are eligible if receiving effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration
• Patients with known chronic hepatitis B virus (HBV) infection are eligible if HBV DNA is undetectable when measured within 6 months prior to registration
• Patients with a known history of hepatitis C virus (HCV) infection are eligible if HCV RNA is undetectable when measured at least 12 weeks after completion of antiviral therapy
• Patients with known history or current symptoms of cardiac disease are eligible if the New York Heart Association Functional Classification is class I or II
• Patients with a known history of congenital long QT syndrome are ineligible
• Patients with known DPD deficiency are ineligible
• \* NON-PATIENT (ONCOLOGY PHYSICIAN OR ONCOLOGY ADVANCED PRACTICE PROVIDER ELIGIBILITY:

• 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
• The non-patient participant must be proficient in the English language
• The non-patient participant must be age 21 years or older

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Health services research

Study locations

United States · 355 centers

• Fairbanks Memorial Hospital — Fairbanks
• Cancer Center at Saint Joseph's — Phoenix
• Mercy Hospital Fort Smith — Fort Smith
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro — Jonesboro
• CARTI Cancer Center — Little Rock
• Mission Hope Medical Oncology - Arroyo Grande — Arroyo Grande
• Mercy Cancer Center - Carmichael — Carmichael
• Mercy San Juan Medical Center — Carmichael
• … and 347 more centers

Puerto Rico · 7 centers

Center list to be confirmed — check the primary protocol.

Guam · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07283939 · A232402CD · NCI-2025-04689

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗