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

Sponsor
Changhoon Yoo (Other)
Overall Status
Completed
CT.gov ID
NCT03524508
Collaborator
Ulsan University Hospital (Other), Chungnam National University Hospital (Other), Kyungpook National University Chilgok Hospital (Other), Inje University (Other)
178
Enrollment
1
Location
2
Arms
39.9
Actual Duration (Months)
4.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
178 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 4, 2018
Actual Primary Completion Date :
Sep 30, 2020
Actual Study Completion Date :
Dec 31, 2021

Arms and Interventions

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.

Drug: Onivyde
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

    • Drug: 5-FU/LV
    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.

    Drug: 5-FU/LV
    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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival by independent central reviewer [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.

    Secondary Outcome Measures

    1. Overall Survival [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

    2. Response rates determined by the investigator according to the RECIST(Response Evaluation Criteria in Solid Tumors) v1.1 [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)

    3. EORTC-QLQ (European Organization for Research and Treatment of Cancer - Quality of life Questionnaire) C30 (version 3.0) [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.

    4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [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

    5. Progression Free Survival by investigator assessment [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.

    6. Response rates determined by the independent central reviewer [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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. ECOG performance status 2-4

    2. Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment

    3. Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2

    4. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months

    5. 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

    6. Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health

    7. Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors

    8. Known hypersensitivity to any of the components of Onivyde other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.

    9. 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.

    10. Previous treatment with combination drug tegafur, gimeracil, and oteracil potassium with seven days before enrollment.

    11. Current treatment with Sorivudine.

    12. Severe fatigue or bone marrow depression after prior radiotherapy or antineoplastic therapy

    13. Pregnancy or women with child-bearing potential or lactating

    14. Non-malignant severe co-morbidity

    15. Previous second-line anti-cancer therapy (e.g., Tegafur)

    16. 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)

    17. History or current eveidence of brain metastasis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Asan Medical Center Seoul Korea, Republic of 05505

    Sponsors and Collaborators

    • Changhoon Yoo
    • Ulsan University Hospital
    • Chungnam National University Hospital
    • Kyungpook National University Chilgok Hospital
    • Inje University

    Investigators

    • Principal Investigator: Changhoon Yoo, Asan Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Changhoon Yoo, Assistant Professor, Asan Medical Center
    ClinicalTrials.gov Identifier:
    NCT03524508
    Other Study ID Numbers:
    • NIFTY
    First Posted:
    May 14, 2018
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Biliary Tract Neoplasms
    Fluorouracil
    Irinotecan

    Study Results

    No Results Posted as of Aug 24, 2022