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CholangiocarcinomaPhase 2TRITICCNCT04059562

Trifluridine/Tipiracil in Combination With Irinotecan as a Second Line Therapy in Patients With Cholangiocarcinoma

A Phase 2 study testing Combination of Lonsurf® and Irinotecan in people with Cholangiocarcinoma, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.

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

This is a prospective, single arm, open label, non-randomized, exploratory, multi-centre pilot study with median progression free survival as primary outcome. In total 28 patients (including 3 calculated drop outs and invalid cases) with advanced cholangiocellular carcinoma after failure of a gemcitabine based… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma
What is being tested?
Combination of Lonsurf® and Irinotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteGermany
Study dates
28 Oct 2021to 8 Jan 2024
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent incl. participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) prior to performing any protocol-related procedures, including screening evaluations
  • Age ≥ 18 years at time of study entry
  • Histologically or cytologically confirmed, non-resectable, locally advanced or metastatic cholangiocarcinoma or gall bladder carcinoma
  • Measurable or assessable disease according to RECIST 1.1
  • Documented disease progression after prior gemcitabine or gemcitabine containing therapy. Examples of permitted therapies include, but are not limited to: a) Single agent gemcitabine); b) Any gemcitabine-based regimen, with or without maintenance gemcitabine
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Show all 16Show fewer
  • Ability to take medications orally
  • Adequate blood count, liver-enzymes, and renal function:
  • Absolute neutrophil count (ANC) > 1,500 cells/μL without the use of hematopoietic growth factors; and Platelet count ≥ 100 x 109/L (>100,000 per mm3) and Hemoglobin > 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)
  • Serum total bilirubin ≤ 1.5x upper normal limit (ULN) (biliary drainage is allowed for biliary obstruction; elevated bilirubin should be caused by obstruction not impaired liver function as assessed by albumin and international normalised ratio (INR) values):
  • Albumin levels ≥ 3.0 g/dL
  • Patients not receiving therapeutic anticoagulation must have an INR< 1.5 ULN and partial thromboplastin time (PTT) < 1.5 ULN within 7 days prior to inclusion. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion.
  • aspartate aminotransferase (AST) (SGOT) and Alanine transaminase (ALT) (SGPT) ≤ 5 x institutional upper limit of normal
  • Serum Creatinine ≤ 1.5 x ULN and a calculated glomerular filtration rate ≥ 30 mL per minute Adequate renal and bone marrow function
  • In case of liver cirrhosis: Child-Pugh A
  • Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control

Who cannot join

  • Age < 18 years
  • Central nerve system (CNS) metastases
  • Active, uncontrolled infection
  • Additional malignancy within the past 2 years (except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer)
  • Clinically significant gastrointestinal disorders including bleeding, inflammation, occlusion, or diarrhea > grade 1
  • Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Show all 14Show fewer
  • Known hypersensitivity to Trifluridine/Tipiracil or Camptothecin (CPT)-11 or their components
  • Medication that is known to interfere with any of the agents applied in the trial
  • Pregnancy or lactating female
  • Prior partial or total gastrectomy
  • Previous radio- or radiochemotherapy, previous transarterial chemoembolisation (TACE), radiofrequency ablation (RFA) or selective intraarterial radiotherapy (SIRT) within 3 months prior to inclusion (except radiation for bone metastases)
  • Patients who might be dependent on the sponsor, site or the investigator
  • Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a German drug law (AMG)].

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Klinik für Gastroenterologie, Hepatologie und Infektiologie

    Düsseldorf, North Rhine-Westphalia, 40225

Other trials in Germany

About this study

Official title: Efficacy and Safety of Trifluridine/Tipiracil in Combination With Irinotecan as a Second Line Therapy in Patients With Cholangiocarcinoma

This is a prospective, single arm, open label, non-randomized, exploratory, multi-centre pilot study with median progression free survival as primary outcome.

In total 28 patients (including 3 calculated drop outs and invalid cases) with advanced cholangiocellular carcinoma after failure of a gemcitabine based first-line therapy will be enrolled at 5 centres.

Read more

To examine the efficacy of a combination therapy of Trifluridine/Tipiracil and Irinotecan in patients with advanced, non resectable or metastatic cholangio- and gallbladder carcinoma after failure to respond to a previous gemcitabine treatment.

The study will be accompanied by a translational research program:

Before treatment and after each radiological tumor assessment (Q6W) blood and stool will be collected and extensive panels of biomarkers will be accessed.

Read the detailed description

This is a prospective, single arm, open label, non-randomized, exploratory, multi-centre pilot study with median progression free survival as primary outcome.

In total 28 patients (including 3 calculated drop outs and invalid cases) with advanced cholangiocellular carcinoma after failure of a gemcitabine based first-line therapy will be enrolled at 5 centres.

To examine the efficacy of a combination therapy of Trifluridine/Tipiracil and Irinotecan in patients with advanced, non resectable or metastatic cholangio- and gallbladder carcinoma after failure to respond to a previous gemcitabine treatment.

The study will be accompanied by a translational research program:

Before treatment and after each radiological tumor assessment (Q6W) blood and stool will be collected and extensive panels of biomarkers will be accessed.

Patients will be treated until radiological progression. In average this will be about 4 months. A follow up is planned every 3 months up to 6 months to asses life quality and progression data.

Being tested
Combination of Lonsurf® and Irinotecan
Medical subject headings
Cholangiocarcinoma

What participants receive

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

  • Combination of Lonsurf® and IrinotecanCombination product

    Trifluridine/Tipiracil (Lonsurf®) and Irinotecan

    • Trifluridine/Tipiracil will be administered at a dose of 25 mg/m2 / dose twice daily on days 1-5 followed by a 9-days recovery period from day 6 trough day 14 of each 14-days treatment cycle.
    • Irinotecan will be administered at the same time as Trifluridine/Tipiracil (Lonsurf®) on day 1 of each cycle at a dose of 180 mg/m2 / dose.
Study groups in NCT04059562
Study groupRoleWhat they receive
TreatmentExperimentalCombination of Lonsurf® and Irinotecan
Receives: Combination Product: Combination of Lonsurf® and Irinotecan

What is being measured

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

  1. Median progression free survival (PFS)

    Median progression free survival (PFS)

    Measured: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

Secondary outcomes (6)

  1. Progression-free survival rate

    Progression-free survival rate @ 4 months defined as the proportion of patients with non-progressive disease 4 months after inclusion by intention to treat analysis

    Measured: At 4 months

  2. Median overall survival

    Median overall survival

    Measured: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

  3. Response according to RECIST 1.1

    Proportion of patients with an objective response according to RECIST 1.1

    Measured: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

  4. Safety (type, grade and frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs))

    Safety (type, grade and frequency of AEs/SAEs)

    Measured: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

  5. Quality of life - European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-30)

    Analysis of quality of life (EORTC QLQ-30)

    Measured: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

  6. Quality of life - EuroQol-5Dimensions-3Levels (EQ-5D-5L) questionnaires

    Analysis of quality of life (EQ-5D-5L questionnaires)

    Measured: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

Timeline

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

  1. First posted16 Aug 2019
  2. Study start28 Oct 2021
  3. Primary completion8 Jan 2024
  4. Study completion8 Jan 2024

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
Not applicable
Intervention model
Single group
Model description
Combination of Lonsurf® and Irinotecan in 28 patients with cholangiocarcinoma.
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04059562
Sponsor's protocol ID
17-157
Acronym
TRITICC
Status last verified
Mar 2024
First submitted
4 Sep 2018
Last updated
27 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Plentz RR, Malek NP. Clinical presentation, risk factors and staging systems of cholangiocarcinoma. Best Pract Res Clin Gastroenterol. 2015 Apr;29(2):245-52. doi: 10.1016/j.bpg.2015.02.001. Epub 2015 Feb 14.

    PubMed 25966425

  • Muller RK. [Documentation of forensic-chemical studies on punched cards]. Dtsch Z Gesamte Gerichtl Med. 1966;58(1):65-75. No abstract available. German.

    PubMed 5966423

  • Blechacz BR, Gores GJ. Cholangiocarcinoma. Clin Liver Dis. 2008 Feb;12(1):131-50, ix. doi: 10.1016/j.cld.2007.11.003.

    PubMed 18242501

  • 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 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

  • Walter T, Horgan AM, McNamara M, McKeever L, Min T, Hedley D, Serra S, Krzyzanowska MK, Chen E, Mackay H, Feld R, Moore M, Knox JJ. Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study. Eur J Cancer. 2013 Jan;49(2):329-35. doi: 10.1016/j.ejca.2012.08.003. Epub 2012 Sep 1.

    PubMed 22947649

  • 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

  • Guion-Dusserre JF, Lorgis V, Vincent J, Bengrine L, Ghiringhelli F. FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma. World J Gastroenterol. 2015 Feb 21;21(7):2096-101. doi: 10.3748/wjg.v21.i7.2096.

    PubMed 25717243

  • Petrelli F, Inno A, Ghidini A, Rimassa L, Tomasello G, Labianca R, Barni S; GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente) and Cremona Hospital. Second line with oxaliplatin- or irinotecan-based chemotherapy for gemcitabine-pretreated pancreatic cancer: A systematic review. Eur J Cancer. 2017 Aug;81:174-182. doi: 10.1016/j.ejca.2017.05.025.

    PubMed 28633088

  • Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S, Rustum YM. Irinotecan in the treatment of colorectal cancer: clinical overview. J Clin Oncol. 2001 Mar 1;19(5):1501-18. doi: 10.1200/JCO.2001.19.5.1501.

    PubMed 11230497

  • Burris HA 3rd, Fields SM. Topoisomerase I inhibitors. An overview of the camptothecin analogs. Hematol Oncol Clin North Am. 1994 Apr;8(2):333-55.

    PubMed 8040144

  • Toffoli G, Cecchin E, Corona G, Boiocchi M. Pharmacogenetics of irinotecan. Curr Med Chem Anticancer Agents. 2003 May;3(3):225-37. doi: 10.2174/1568011033482477.

    PubMed 12769780

  • Irinotecan. 2025 Jan 15. Drugs and Lactation Database (LactMed(R)) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500877/

    PubMed 29999936

  • Emura T, Murakami Y, Nakagawa F, Fukushima M, Kitazato K. A novel antimetabolite, TAS-102 retains its effect on FU-related resistant cancer cells. Int J Mol Med. 2004 Apr;13(4):545-9.

    PubMed 15010854

  • Emura T, Suzuki N, Yamaguchi M, Ohshimo H, Fukushima M. A novel combination antimetabolite, TAS-102, exhibits antitumor activity in FU-resistant human cancer cells through a mechanism involving FTD incorporation in DNA. Int J Oncol. 2004 Sep;25(3):571-8.

    PubMed 15289858

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Combination of Lonsurf® and Irinotecan in people with Cholangiocarcinoma, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.

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 16 inclusion and 14 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 27 Mar 2024. 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 Germany. 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?

Median progression free survival (PFS) (time frame: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)). 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 NCT04059562, which also lists 29 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 27 Mar 2024.

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