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Metastatic Biliary Tract CancerPhase 2NCT03524508

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

A Phase 2 study testing Onivyde and 5-FU/LV in people with Metastatic Biliary Tract Cancer, run by Changhoon Yoo at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Metastatic Biliary Tract Cancer
What is being tested?
Onivyde and 5-FU/LV
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
178 participants
Where
1 siteSouth Korea
Study dates
4 Sep 2018to 31 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and written informed consent form
  • ≥ 19 years of age
  • Histologically or cytologically confirmed cholangiocarcinoma
  • Documented metastatic disease
  • At least one measurable lesion according to the RECIST v1.1
  • Disease progression on gemcitabine-cisplatin combination therapy
Show all 9Show fewer
  • 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.
  • Adequate hepatic, renal and hematological function AST(Aspartate Aminotransferase), ALT(Alanine Aminotransferase) ≤ 100 IU/L (100 U/L), Cr(Creatinine) ≤ 1.5mg/dL
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-1

Who cannot join

  • Serum total bilirubin ≥2 x ULN(upper limit of normal) (biliary drainage is allowed for biliary obstruction)
  • Severe renal impairment (Clcr ≤ 30 ml/min)
  • 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
Show all 23Show fewer
  • ECOG performance status 2-4
  • Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment
  • Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2
  • Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
  • 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
  • Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health
  • Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
  • Known hypersensitivity to any of the components of Onivyde other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
  • 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.
  • Previous treatment with combination drug tegafur, gimeracil, and oteracil potassium with seven days before enrollment.
  • Current treatment with Sorivudine.
  • Severe fatigue or bone marrow depression after prior radiotherapy or antineoplastic therapy
  • Pregnancy or women with child-bearing potential or lactating
  • Non-malignant severe co-morbidity
  • Previous second-line anti-cancer therapy (e.g., Tegafur)
  • 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)
  • History or current eveidence of brain metastasis

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

About this study

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

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.

Read the 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.

Being tested
Onivyde, 5-FU/LV
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OnivydeDrug

    Also called Liposomal irinotecan

    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.

  • 5-FU/LVDrug

    Also called Fluorouracil/Folinic acid

    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

Study groups in NCT03524508
Study groupRoleWhat they receive
5-FU/LV/OnivydeExperimentalOnivyde 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.
Receives: Drug: Onivyde; Drug: 5-FU/LV
5FU/LVActive comparatordl-LV 400mg/m2 or l-LV 200mg/m2 (30 minutes), 5-FU 2400 mg/m2 (46 hours) IV every 2 weeks.
Receives: Drug: 5-FU/LV

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival by independent central reviewer

    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.

    Measured: 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 outcomes (6)

  1. Overall Survival

    Overall survival is the time from the date of enrollment to death from any cause

    Measured: from the date of enrollment to death from any cause. (assessed up to 36 months)

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

    The response rate is the proportion of eligible patients with measurable lesions with a overall response of CR(Complete Response) or PR(Partial Response)

    Measured: from the date of enrollment to end of treatment. (assessed up to 36 months)

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

    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.

    Measured: from the date of Screening to end of treatment. (assessed up to 36 months)

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

    Severity of adverse events will be graded by NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v4.03

    Measured: from the date of enrollment to 30 days after last treatment. (assessed up to 36 months)

  5. Progression Free Survival by investigator assessment

    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.

    Measured: from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months)

  6. Response rates determined by the independent central reviewer

    The response rate is the proportion of eligible patients with measurable lesions with a overall response of CR(Complete Response) or PR(Partial Response)

    Measured: from the date of enrollment to end of treatment. (assessed up to 36 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2018
  2. Study start4 Sep 2018
  3. Primary completion30 Sep 2020
  4. Study completion31 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
178 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03524508
Sponsor's protocol ID
NIFTY
Status last verified
Aug 2022
First submitted
18 Apr 2018
Last updated
24 Aug 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. doi: 10.3322/caac.21332. Epub 2016 Jan 7.

    PubMed 26742998

  • Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010 Jun;17(6):1471-4. doi: 10.1245/s10434-010-0985-4.

    PubMed 20180029

  • Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

    PubMed 20375404

  • Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, Nagino M, Kondo S, Nagaoka S, Funai J, Koshiji M, Nambu Y, Furuse J, Miyazaki M, Nimura Y. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010 Aug 10;103(4):469-74. doi: 10.1038/sj.bjc.6605779. Epub 2010 Jul 13.

    PubMed 20628385

  • Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D; ESMO Guidelines Committee. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v28-v37. doi: 10.1093/annonc/mdw324. No abstract available.

    PubMed 27664259

  • Kim BJ, Hyung J, Yoo C, Kim KP, Park SJ, Lee SS, Park DH, Song TJ, Seo DW, Lee SK, Kim MH, Park JH, Cho H, Ryoo BY, Chang HM. Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: retrospective analysis of 740 patients. Cancer Chemother Pharmacol. 2017 Jul;80(1):209-215. doi: 10.1007/s00280-017-3353-2. Epub 2017 Jun 8.

    PubMed 28597043

  • Fornaro L, Cereda S, Aprile G, Di Girolamo S, Santini D, Silvestris N, Lonardi S, Leone F, Milella M, Vivaldi C, Belli C, Bergamo F, Lutrino SE, Filippi R, Russano M, Vaccaro V, Brunetti AE, Rotella V, Falcone A, Barbera MA, Corbelli J, Fasola G, Aglietta M, Zagonel V, Reni M, Vasile E, Brandi G. Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer. Br J Cancer. 2014 Apr 29;110(9):2165-9. doi: 10.1038/bjc.2014.190. Epub 2014 Apr 8.

    PubMed 24714745

  • Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014 Dec;25(12):2328-2338. doi: 10.1093/annonc/mdu162. Epub 2014 Apr 25.

    PubMed 24769639

  • Brieau B, Dahan L, De Rycke Y, Boussaha T, Vasseur P, Tougeron D, Lecomte T, Coriat R, Bachet JB, Claudez P, Zaanan A, Soibinet P, Desrame J, Thirot-Bidault A, Trouilloud I, Mary F, Marthey L, Taieb J, Cacheux W, Lievre A. Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Enterologues Oncologues. Cancer. 2015 Sep 15;121(18):3290-7. doi: 10.1002/cncr.29471. Epub 2015 Jun 5.

    PubMed 26052689

  • Kim BJ, Yoo C, Kim KP, Hyung J, Park SJ, Ryoo BY, Chang HM. Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients. Br J Cancer. 2017 Feb 28;116(5):561-567. doi: 10.1038/bjc.2016.446. Epub 2017 Jan 12.

    PubMed 28081540

  • Innocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramirez J, Relling M, Chen P, Das S, Rosner GL, Ratain MJ. Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol. 2009 Jun 1;27(16):2604-14. doi: 10.1200/JCO.2008.20.6300. Epub 2009 Apr 6.

    PubMed 19349540

  • Bellanti F, Kagedal B, Della Pasqua O. Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma? Eur J Clin Pharmacol. 2011 May;67 Suppl 1(Suppl 1):87-107. doi: 10.1007/s00228-010-0966-3. Epub 2011 Feb 2.

    PubMed 21287160

  • Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res. 2001 Aug;7(8):2182-94.

    PubMed 11489791

  • Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 1991 Aug 15;51(16):4187-91.

    PubMed 1651156

  • Garcia-Carbonero R, Supko JG. Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res. 2002 Mar;8(3):641-61.

    PubMed 11895891

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Onivyde and 5-FU/LV in people with Metastatic Biliary Tract Cancer, run by Changhoon Yoo at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03524508, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.

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