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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03524508
Recruitment Status : Completed
First Posted : May 14, 2018
Last Update Posted : August 24, 2022
Sponsor:
Collaborators:
Ulsan University Hospital
Chungnam National University Hospital
Kyungpook National University Chilgok Hospital
Inje University
Information provided by (Responsible Party):
Changhoon Yoo, Asan Medical Center

Tracking Information
First Submitted Date  ICMJE April 18, 2018
First Posted Date  ICMJE May 14, 2018
Last Update Posted Date August 24, 2022
Actual Study Start Date  ICMJE September 4, 2018
Actual Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2020)		 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 11, 2018)		 Progression Free Survival [ 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2021)
  • 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
  • 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)
  • 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.
  • 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
  • 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.
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2018)
  • 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
  • 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)
  • 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.
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nal-IRI(Nanoliposomal Irinotecan) Plus 5-FU/LV in Metastatic Biliary Tract Cancer
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Biliary Tract Cancer
Intervention  ICMJE
  • 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 Name: 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 Name: Fluorouracil/Folinic acid
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Onivyde
    • Drug: 5-FU/LV
  • 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.
    Intervention: Drug: 5-FU/LV
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 9, 2020)		 178
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2018)		 174
Actual Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03524508
Other Study ID Numbers  ICMJE NIFTY
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Changhoon Yoo, Asan Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Changhoon Yoo
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Ulsan University Hospital
  • Chungnam National University Hospital
  • Kyungpook National University Chilgok Hospital
  • Inje University
Investigators  ICMJE
Principal Investigator: Changhoon Yoo Asan Medical Center
PRS Account Asan Medical Center
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP