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2 Versus 6 Hour Oxaliplatin Infusions in Patients With Gastrointestinal Cancers

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ClinicalTrials.gov Identifier: NCT03800693
Recruitment Status : Recruiting
First Posted : January 11, 2019
Last Update Posted : May 23, 2019
Sponsor:
Collaborators:
Hematology/Oncology Pharmacy Association
University of Pittsburgh
Information provided by (Responsible Party):
R. Donald Harvey, PharmD, Emory University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Malignant Digestive System Neoplasm Drug: Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Evaluation of the Effect of 2 Versus 6 Hour Oxaliplatin Infusions on Neuropathy and Pharmacokinetics in Patients With Gastrointestinal Cancers
Actual Study Start Date : March 14, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine


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 Name: Folinic acid

Drug: Oxaliplatin
Given IV
Other Name: 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 Name: Folinic acid

Drug: Oxaliplatin
Given IV
Other Name: Eloxatin




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline up to 60 days (course 4) ]
    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.


Secondary Outcome Measures :
  1. Maximum concentrations achieved (Cmax) [ Time Frame: At baseline and at 1, 2, 4, 6, 48, and 192 hours after initiation of oxaliplatin ]
    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.

  2. Changes in tumor size [ Time Frame: Up to 18 months after completion or discontinuation of chemotherapy ]
    The study will assess changes in tumor size per standard of care assessments at screening and every 2 months.

  3. Duration of therapy [ Time Frame: Up to 18 months after completion or discontinuation of chemotherapy ]
    Duration of therapy will be recorded.

  4. Dose density [ Time Frame: Up to 18 months after completion or discontinuation of chemotherapy ]
    Dose density will be recorded.

  5. Frequency of dose holds or reductions [ Time Frame: Up to 18 months after completion or discontinuation of chemotherapy ]
    Frequency of dose holds or reductions will be recorded.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 anticancer therapies within 4 weeks 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 3 weeks 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03800693


Contacts
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Contact: R. Donald Harvey, PharmD 404-778-4381 rdharve@emory.edu
Contact: Amber Draper, PharmD amber.draper@emoryhealthcare.org

Locations
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United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Swathi Chinaranagari    404-686-0239    swathi.chinaranagari@emory.edu   
Contact: Shabnam Montazeri    404-686-0242    shabnam.montazeri@emory.edu   
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Sheena Abraham    404-778-2670    sheena.abraham@emory.edu   
Contact: Samantha Hamilton, RN, BSN    404-778-1801    samantha.jane.hamilton@emory.edu   
Emory Saint Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Alicia Escobar    678-843-7029    alicia.m.escobar@emory.edu   
Contact: Krystal Reese    678-843-5911    krystal.reese@emory.edu   
Sponsors and Collaborators
Emory University
Hematology/Oncology Pharmacy Association
University of Pittsburgh
Investigators
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Principal Investigator: R. Donald Harvey, PharmD Emory University

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Responsible Party: R. Donald Harvey, PharmD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03800693     History of Changes
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 )
First Posted: January 11, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Oxaliplatin
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Fluorouracil
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs