2 Versus 6 Hour Oxaliplatin Infusions in Patients With Gastrointestinal Cancers

Phase II Evaluation of the Effect of 2 Versus 6 Hour Oxaliplatin Infusions on Neuropathy and Pharmacokinetics in Patients With Gastrointestinal Cancers

This phase II trial studies how well giving oxaliplatin over 6 hours works in treating nerve damage in patients with gastrointestinal cancers. Oxaliplatin can cause side effects such as nerve damage that may delay or reduce the dose of oxaliplatin. Giving oxaliplatin over a longer period of time (6 hours) may prevent or delay the development of nerve damage, which may keep patients on standard doses of chemotherapy longer, without having to delay treatment.

Study Overview

• Status: Recruiting
• Conditions: Malignant Digestive System Neoplasm
• Intervention / Treatment: Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the effect of 2 versus 6-hour oxaliplatin infusion time on the difference in severity of sensory neuropathy as measured by patient reported outcome (PRO) scores on the European Organization for Research and Treatment of Cancer (EORTC) chemotherapy-induced peripheral neuropathy (CIPN-20) scale at the initiation of cycle 4.

SECONDARY OBJECTIVES:

I. Pharmacokinetic parameters of maximum concentration (Cmax), area under the curve (AUC), time of maximum concentration (tmax), clearance, and half life (t1/2) of platinum ultra-filtrate.

II. CIPN-20 sensory score changes over the duration of therapy as measured by a cumulative area-under-the curve score.

III. Clinical outcomes including duration of therapy, oxaliplatin dose reductions, delays in therapy, and overall dose intensity and delivery of oxaliplatin.

IV. Relationship between oxaliplatin Cmax, patient-reported acute neurotoxicity, and chronic neurotoxicity by CIPN-20 scores.

OUTLINE: Patients are randomized to 1 of 2 groups.

2-hour infusion group: Patients receive oxaliplatin intravenously (IV) and leucovorin IV over 2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

6-hour infusion group: Patients receive oxaliplatin IV over 6 hours on day 1. Patients also receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 3, 6, 12, and 18 months.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amber Draper, PharmD; Email: amber.draper@emoryhealthcare.org
• Study Contact Backup: Name: Olumide B. Gbolahan, MBBS, MSc; Phone Number: 404-778-0032; Email: ogbolah@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Contact: Allyson Anderson; Phone Number: 404-686-0239; Email: allyson.anderson@emory.edu
      • Principal Investigator: Olumide B. Gbolahan, MBBS, MSc
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University Hospital Midtown
      • Contact: Autumn Lunceford; Phone Number: 404-686-1638; Email: patricia.autumn.lee.lunceford@emory.edu
      • Principal Investigator: Olumide B. Gbolahan, MBBS, MSc
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Emory Saint Joseph's Hospital
      • Contact: Alicia Escobar; Phone Number: 678-843-7029; Email: alicia.m.escobar@emory.edu
      • Principal Investigator: Olumide B. Gbolahan, MBBS, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Confirmed diagnosis of a gastrointestinal cancer
• Plan for 4 or more cycles of FOLFOX6 (fluorouracil [with leucovorin] and oxaliplatin) containing chemotherapy
• Histologically confirmed, measurable or evaluable disease. Patients with advanced or metastatic disease should have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients in the adjuvant treatment setting planned to have > 4 cycles of FOLFOX-containing chemotherapy are eligible and will be followed per standard of care
• Absolute neutrophil count (ANC) ≥ 1,500/µL (no white blood cell growth factors allowed to meet requirement)
• Platelets ≥ 75,000/µL (may be transfused up to 72 hours prior to day 1 to meet requirement)
• Hemoglobin ≥ 8 g/dL (may be transfused up to 72 hours prior to day 1 to meet requirement)
• Creatinine clearance > 30 mL/min by Cockcroft-Gault, to preserve similar dosing (85 mg/m²) for analysis
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Signed informed consent
• Adequate birth control when appropriate

Exclusion Criteria:

• Any preexisting grade 2 or higher peripheral neuropathy
• Patients currently receiving anticancer therapies or who have received any focal or systemic anticancer therapy within 14days of the start of FOLFOX6
• Known intolerance or hypersensitivity to any agent in FOLFOX6 or concurrent agents

• Patients who have any known severe and/or uncontrolled medical conditions such as:

  • Unstable angina pectoris, symptomatic heart failure; (New York Heart Association class III or IV), myocardial infarction ≤ 6 months prior, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
  • Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, or decompensated liver disease
• Patients with any history of severe hemorrhage requiring ≥ 4 units of packed red blood cells (RBCs) in a 48-hour period
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
• Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 14days prior to dosing
• Pregnant or nursing (lactating) women

• Women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include combination of any two of the following:

  • Use of oral, injected or implanted hormonal methods of contraception or;
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS);
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
  • Total abstinence or;
  • Male/female sterilization Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2-hour infusion group; Patients receive oxaliplatin IV and leucovorin IV over 2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Fluorouracil; Given IV; Other Names: 5-FU; Carac; Ribofluor; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: Eloxatin
Experimental: 6-hour infusion group; Patients receive oxaliplatin IV over 6 hours on day 1. Patients also receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Fluorouracil; Given IV; Other Names: 5-FU; Carac; Ribofluor; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of 2 versus 6-hour oxaliplatin infusion time on neuropathy as measured by patient reported outcome (PRO) scores on the European Organization for Research and Treatment of Cancer (EORTC) chemotherapy-induced peripheral neuropathy (CIPN-20) scale	The EORTC-CIPN-20 sub-scales will be computed according to the standard scoring algorithm and then transformed to a 0 to 100 scale, where high scores mean less symptom burden. The primary outcome measure of difference in sensory scores of the two groups between baseline and the initiation of cycle 4 will be the driver of the analysis.	Baseline up to 60 days (course 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentrations achieved (Cmax)	The study will focus on maximum concentrations achieved (Cmax) with each infusion time. Data will be analyzed using non-compartmental methods via Phoenix WinNonlin analytical software, version 8.0 or higher.	At baseline and at 1, 2, 4, 6, 48, and 192 hours after initiation of oxaliplatin
Changes in tumor size	The study will assess changes in tumor size per standard of care assessments at screening and every 2 months.	Up to 18 months after completion or discontinuation of chemotherapy
Duration of therapy	Duration of therapy will be recorded.	Up to 18 months after completion or discontinuation of chemotherapy
Dose density	Dose density will be recorded.	Up to 18 months after completion or discontinuation of chemotherapy
Frequency of dose holds or reductions	Frequency of dose holds or reductions will be recorded.	Up to 18 months after completion or discontinuation of chemotherapy

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: University of Pittsburgh; Hematology/Oncology Pharmacy Association
• Investigators: Principal Investigator: Olumide B. Gbolahan, MBBS, MSc, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Estimated): August 5, 2026
• Study Completion (Estimated): September 17, 2026

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (Actual): January 11, 2019

Study Record Updates

• Last Update Posted (Estimated): November 6, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin
• Other Study ID Numbers: IRB00106610; NCI-2018-02241 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); Winship4468-18 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No