Nal-IRI(Nanoliposomal Irinotecan) Plus 5-FU/LV in Metastatic Biliary Tract Cancer

August 22, 2022 updated by: Changhoon Yoo

Randomized Phase II Trial of Fluorouracil and Folinic Acid With or Without Liposomal Irinotecan (ONIVYDE) for Patients With Metastatic Biliary Tract Cancer Which Progressed Following Gemcitabine Plus Cisplatin

The purpose of this study is to evaluate the efficacy and safety of combination of fluorouracil/folinic acid and liposomal irinotecan(Onivyde) compared with fluoruracil/folinic acid in patients with metastatic biliary tract cancer which progressed on 1st line gemcitabine/cisplatin.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This study is a multicenter, open-label, randomized, phase II study comparing the efficacy and safety between fluorouracil/folinic acid plus liposomal irinotecan and fluoruracil/folinic acid monotherapy in patients with metastatic biliary tract cancer which progressed on 1st line gemcitabine/cisplatin.

Eligible patients will be included in this study and treated according to the protocol. Study treatment will be continued until disease progression, unacceptable toxicity, or patient's decision/consent withdrawal. Local investigators will determine disease progression, radiologic or clinical deterioration.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed and written informed consent form
  2. ≥ 19 years of age
  3. Histologically or cytologically confirmed cholangiocarcinoma
  4. Documented metastatic disease
  5. At least one measurable lesion according to the RECIST v1.1
  6. Disease progression on gemcitabine-cisplatin combination therapy
  7. For patients whose disease recurred after curative resection (R0 or R1), previous adjuvant 5-FU-based chemotherapy is allowed if there is at least 6 month-interval between the last dose of adjuvant chemotherapy and recurrence of disease.
  8. Adequate hepatic, renal and hematological function AST(Aspartate Aminotransferase), ALT(Alanine Aminotransferase) ≤ 100 IU/L (100 U/L), Cr(Creatinine) ≤ 1.5mg/dL
  9. Eastern Cooperative Oncology Group (ECOG) Performance status 0-1

Exclusion Criteria:

  1. Serum total bilirubin ≥2 x ULN(upper limit of normal) (biliary drainage is allowed for biliary obstruction)
  2. Severe renal impairment (Clcr ≤ 30 ml/min)
  3. Inadequate bone marrow reserves as evidenced by:

    • ANC(Absolute Neutrophile Count) ≤ 1,500 cells/μl; or
    • Platelet count ≤ 100,000 cells/μl; or
    • Hemoglobin ≤ 9 g/dL
  4. ECOG performance status 2-4
  5. Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment
  6. Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2
  7. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
  8. NYHA(New York Heart Association) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
  9. Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health
  10. Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
  11. Known hypersensitivity to any of the components of Onivyde other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
  12. Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use an effective method of contraception, during therapy and for 3 months following the last dose of Onivyde. Females of Childbearing Potential must either agree to use and be able to take effective contraceptive birth control measures (Pearl Index < 1) or agree to practice complete abstinence from heterosexual intercourse during the course of the study and for at least 3 months after last application of program treatment. A female subject is considered to be of childbearing potential unless she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 years, or unless she is surgically sterile. Males must agree not to father a child (including not donating sperm) during the course of the trial and for at least 6 months after last administration of study drugs.
  13. Previous treatment with combination drug tegafur, gimeracil, and oteracil potassium with seven days before enrollment.
  14. Current treatment with Sorivudine.
  15. Severe fatigue or bone marrow depression after prior radiotherapy or antineoplastic therapy
  16. Pregnancy or women with child-bearing potential or lactating
  17. Non-malignant severe co-morbidity
  18. Previous second-line anti-cancer therapy (e.g., Tegafur)
  19. History of other malignancy with a disease-free interval <5 years (Registration is permitted if it has minimal impact on prognosis, such as carcinoma in situ and papillary thyroid cancer)
  20. History or current eveidence of brain metastasis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 5-FU/LV/Onivyde
Onivyde 70 mg/m2 (90 minutes), dl-LV 400mg/m2 or l-LV 200mg/m2 (30 minutes), 5-FU 2400 mg/m2 (46 hours) IV every 2 weeks.
The recommended dose and regimen of Onivyde is 70 mg/m2 intravenously over 90 minutes, followed by dl-LV 400mg/m2 or l-LV 200mg/m2 intravenously over 30 minutes, followed by 5-FU 2400 mg/m2 intravenously over 46 hours, administered every 2 weeks.
Other Names:
  • Liposomal irinotecan
The recommended dose and regimen of dl-LV 400mg/m2 or l-LV 200mg/m2 intravenously over 30 minutes, followed by 5-FU 2400 mg/m2 intravenously over 46 hours, administered every 2 weeks
Other Names:
  • Fluorouracil/Folinic acid
Active Comparator: 5FU/LV
dl-LV 400mg/m2 or l-LV 200mg/m2 (30 minutes), 5-FU 2400 mg/m2 (46 hours) IV every 2 weeks.
The recommended dose and regimen of dl-LV 400mg/m2 or l-LV 200mg/m2 intravenously over 30 minutes, followed by 5-FU 2400 mg/m2 intravenously over 46 hours, administered every 2 weeks
Other Names:
  • Fluorouracil/Folinic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival by independent central reviewer
Time Frame: from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months)
Progression-free survival is the time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.
from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: from the date of enrollment to death from any cause. (assessed up to 36 months)
Overall survival is the time from the date of enrollment to death from any cause
from the date of enrollment to death from any cause. (assessed up to 36 months)
Response rates determined by the investigator according to the RECIST(Response Evaluation Criteria in Solid Tumors) v1.1
Time Frame: from the date of enrollment to end of treatment. (assessed up to 36 months)
The response rate is the proportion of eligible patients with measurable lesions with a overall response of CR(Complete Response) or PR(Partial Response)
from the date of enrollment to end of treatment. (assessed up to 36 months)
EORTC-QLQ (European Organization for Research and Treatment of Cancer - Quality of life Questionnaire) C30 (version 3.0)
Time Frame: from the date of Screening to end of treatment. (assessed up to 36 months)
EORTC-QLQ C-30 questionnaires will be performed at screening visit, at pre-dose (Cycle 1 Day1) of every subsequent cycle, at the end of treatment visit. It is a 30-item questionnaire. It has 4-point scales for the item number 1 to 28. These are coded with the same response categories as items 1 to 28, namely "not at all=1" "a little=2" "quite a bit=3" and "very much=4" It has 7-point scale for question number 29 to 30. These are coded with the same response categories as items 29 to 30, namely "worst=1" to "best=7" Total score will be minimum 30 and maximum 126.
from the date of Screening to end of treatment. (assessed up to 36 months)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: from the date of enrollment to 30 days after last treatment. (assessed up to 36 months)
Severity of adverse events will be graded by NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v4.03
from the date of enrollment to 30 days after last treatment. (assessed up to 36 months)
Progression Free Survival by investigator assessment
Time Frame: from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months)
Progression-free survival is the time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.
from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months)
Response rates determined by the independent central reviewer
Time Frame: from the date of enrollment to end of treatment. (assessed up to 36 months)
The response rate is the proportion of eligible patients with measurable lesions with a overall response of CR(Complete Response) or PR(Partial Response)
from the date of enrollment to end of treatment. (assessed up to 36 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Changhoon Yoo, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 4, 2018

Primary Completion (Actual)

September 30, 2020

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

April 18, 2018

First Submitted That Met QC Criteria

May 11, 2018

First Posted (Actual)

May 14, 2018

Study Record Updates

Last Update Posted (Actual)

August 24, 2022

Last Update Submitted That Met QC Criteria

August 22, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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