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Esophageal CancerPhase 2LyRICXNCT03764553

Liposomal iRInotecan, Carboplatin or oXaliplatin for Esophagogastric Cancer

A Phase 2 study testing Liposomal Irinotecan, Carboplatin and Capecitabine in people with Esophageal Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 34 sites in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a multi-center, open label, randomized phase II trial for patients with previously untreated metastatic or locally advanced esophagogastric cancer, using a pick the winner design to identify the best combination therapy in terms of progression free survival and neurotoxicity. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Cancer
What is being tested?
Liposomal Irinotecan, Carboplatin and Capecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
320 participants
Where
34 sitesNetherlands
Study dates
1 May 2019to 1 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Patients must provide written informed consent according to International Conference on Harmonization (ICH)/Guideline for Good Clinical practice (GCP), and national/local regulations prior to any screening procedures.
  • Male or female adult patients (> 18 years).
  • Patients with histologically confirmed diagnosis of metastatic or irresectable human epidermal growth (HER2) negative adenocarcinoma of the stomach or oesophagus; patients with HER2 positive disease are eligible when treatment with trastuzumab is contraindicated. If histology cannot be obtained, cytology is acceptable to prove metastatic disease.
  • Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is allowed if other untreated lesions eligible for evaluation are present.
  • Measurable disease as assessed by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0-2
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  • Patient has adequate bone marrow and organ function as defined by the following laboratory values:
  • Absolute Neutrophil Count (ANC) > 1.5 x 109 /L
  • Hemoglobin (Hgb) > 5.6 mmol/L
  • Platelets > 100 x 109 /L
  • Serum total bilirubin within ≤ 1.5 x ULN (upper limit of normal); or total bilirubin < 3.0 x upper limit of normal (ULN) with direct bilirubin within normal range in patients with well documented Gilbert's syndrome; biliary drainage is allowed for biliary obstruction
  • Serum creatinine < 1.5 x ULN or creatinine clearance >30 mL/min/1.73 m2
  • Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 2.5x ULN within normal range or < 5.0 x ULN if liver metastases are present
  • If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test, beta-human chorionic gonadotropin (β-hCG) documented 72 hours prior to the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug and after the end of treatment as recommended.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Who cannot join

  • Prior systemic treatment for metastatic or irresectable stomach or oesophageal cancer.
  • Evidence of disease progression within six months after completion of adjuvant or neoadjuvant treatment (whichever is last) containing a fluoropyrimidine and/or platinum compound and/or irinotecan; progression on neoadjuvant chemoradiation with carboplatin area under the curve (AUC2) and paclitaxel 50 mg/m2 within this time frame is allowed.
  • All target lesions in a radiation field without documented disease progression. 11
  • Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
  • Past or current malignancy other than entry diagnosis interfering with prognosis of metastatic esophagogastric cancer.
  • Known uncontrollable hypersensitivity or contraindications to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, leucovorin, oxaliplatin, carboplatin. Patients with previous dose reductions or delays are eligible.
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  • Complete dihydropyrimidine dehydrogenase deficiency .
  • Patient has active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy.
  • Patient has known past or active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
  • Signs of interstitial lung disease (ILD)
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study.
  • Use of other investigational drugs within 30 days of enrollment.
  • Patient is enrolled in any other clinical protocol or investigational trial that will interfere with the primary endpoint.
  • Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol.
  • Current use or any use in last two weeks of strong cytochrome P4503A (CYP3A-enzyme), CYP2C8, and/or strong UDP glucuronosyltransferase (UGT1A) inhibitors/inhibitors
  • Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of study treatment.
  • Treatment within 4 weeks with dihydropyrimidine dehydrogenase (DPD) inhibitors, including sorivudine or its chemically related analogues such as brivudine.
  • Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

Netherlands34 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5223 GZ

  • Ziekenhuisgroep Twente

    Almelo

  • Flevoziekenhuis

    Almere Stad

  • Meander MC

    Amersfoort

  • Academic Medical Center, Medical Oncology

    Amsterdam, 1100 DD

  • Rijnstate Ziekenhuis

    Arnhem, 6815 AD

  • Amphia Ziekenhuis

    Breda, 4818 CK

  • Reinier de Graaf Gasthuis

    Delft, 2625 AD

  • Nij Smellinghe

    Drachten

  • Ziekenhuis Gelderse Vallei

    Ede

  • Catherina Ziekenhuis

    Eindhoven

  • Treant Zorggroep

    Emmen

  • Zuyderland Medisch Centrum

    Geleen

  • Admiraal de Ruijter Ziekenhuis

    Goes, 4460 AA

  • Sint Jansdal

    Harderwijk

  • Elkerliek ziekenhuis

    Helmond

  • Tergooi ziekenhuizen

    Hilversum

  • Spaarne Gasthuis

    Hoofddorp

  • Treant zorggroep

    Hoogeveen, 7909 AA

  • Dijklander ziekenhuis

    Hoorn

  • Medisch Centrum Leeuwarden

    Leeuwarden

  • Leids Universitair Medisch Centrum

    Leiden

  • Sint Antonius Ziekenhuis

    Nieuwegein

  • Canisius Wilherlmina ziekenhuis

    Nijmegen

  • Radboud Universitair Medisch Centrum

    Nijmegen

  • VieCurie

    Roermond, 6043 CV

  • Laurentius Ziekenhuis

    Roermond

  • Bravis ziekenhuis locatie Roosendaal

    Roosendaal, 4708 AE

  • Ikazia ziekenhuis

    Rotterdam

  • Maasstadziekenhuis

    Rotterdam

  • Rivierenland Ziekenhuis

    Rotterdam

  • Haaglanden Medisch Centrum

    The Hague

  • UMCU

    Utrecht, 3508 GA

  • Isala Klinieken

    Zwolle

Other trials in Netherlands

About this study

Official title: Liposomal iRInotecan, Carboplatin or oXaliplatin in the First Line Treatment of Esophagogastric Cancer: a Randomized Phase 2 Study

This is a multi-center, open label, randomized phase II trial for patients with previously untreated metastatic or locally advanced esophagogastric cancer, using a pick the winner design to identify the best combination therapy in terms of progression free survival and neurotoxicity.

Read the detailed description

The sample size to identify the best combination therapy is based on the following decision making strategy. With less or even zero neurotoxicity grade 2-4 (defined as worst toxicity), the Nal-IRI plus 5FU/LV combination is expected to outperform the standard combination capecitabine plus oxaliplatin and may also outperform capecitabine plus carboplatin. To compensate for a higher neurotoxicity grade 2-4 level, the capecitabine combinations should demonstrate increased progression free survival (PFS) according to the next schedule.

With the addition of nivolumab in the second quarter of 2022, the capecitabine combinations are expected to have a PFS benefit over the Nal-IRI of 0.65 months (50% of the 1.7 months seen in the CM6495, because 50% of the capecitabine regimens will be treated with nivolumab)

If the difference in the percentage of patients experiencing neurotoxicity grade 2-4 stays within the 10-30% range, an increase of at least 3.65 months of PFS identifies the most preferable combination strategy; if the percentage is ≤10% and the PFS increase <3.65 months, but in favor of carboplatin, then the choice should be based on other grade 3-4 toxicities observed; otherwise, the strategy with the lowest level of neurotoxicity grade 2-4 is the most preferable one. At least 4.65 months PFS should be gained to compensate for a difference in neurotoxicity grade 2-4 within the >30 to 50% range.

The total number to be included will be 272. Patients will first be tested for PD-L1 and then will be conditionally randomized. Patients with a PD-L1 CPS <5 or a contraindication for nivolumab treatment, will be randomized to respectively the Nal-IRI plus 5FU, the capecitabine plus carboplatin and capecitabine plus oxaliplatin group following a 2:1:1 scheme. Patients with a PD-L1 CPS ≥5 will be randomized to the capecitabine plus carboplatin and capecitabine plus oxaliplatin group following a 2:1 scheme and will receive nivolumab in addition to chemotherapy treatment.

Taking into account 15% withdrawal of patients from the trial before start of study medication, we will include 320 patients.

Being tested
Liposomal Irinotecan, Carboplatin, Capecitabine, Oxaliplatin, 5-fluorouracil
Keywords
palliative chemotherapy, metastatic esophagogastric cancer, Efficacy, toxicity
Medical subject headings
Esophageal Neoplasms

What participants receive

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

Study groups in NCT03764553
Study groupRoleWhat they receive
Liposomal irinotecan, leucovorin and 5FUExperimentalIV Nal-IRI 80 mg/m² (expressed as irinotecan hydrochloride (HCl) salt), folinic acid 400 mg/m², fluorouracil 2400 mg/m² over 46 h, every 2 weeks. No addition of nivolumab is possible for this arm
Receives: Drug: Liposomal Irinotecan; Drug: 5-fluorouracil; Drug: Leucovorin
Carboplatin and capecitabineExperimentalIV and PO Capecitabine 1000 mg/m2 and carboplatin area under the curve (AUC5), every three weeks. In case of PD-L1 CPS ≥5 only: nivolumab, dose according to local standard, iv day 1
Receives: Drug: Carboplatin; Drug: Capecitabine
oxaliplatin and capecitabineExperimentalIV and PO Capecitabine 1000 mg/m2 and oxaliplatin 130 mg/m2, every three weeks. In case of PD-L1 CPS ≥5 only: nivolumab, dose according to local standard, iv day 1
Receives: Drug: Capecitabine; Drug: Oxaliplatin

What is being measured

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

  1. Progression free survival

    To compare the progression free survival

    Measured: 42 months

  2. Number of participants with treatment-related Neurotoxicity

    Number of participants with treatment-related Neurotoxicity according to CTCAE v4.0

    Measured: 42 months

Secondary outcomes (6)

  1. Overall survival

    To determine the overall survival of F-Nal-IRI, capecitabine/Carboplatin (CapCar) and capecitabine/oxaliplatin (CapOx)

    Measured: 54 months

  2. response rate

    To determine the response rate of F-Nal-IRI, CapCar and CapOx

    Measured: 42 months

  3. adverse events

    To determine the adverse events of F-Nal-IRI, CapCar and CapOx according to NCI common toxicity criteria (CTC) version 4

    Measured: 42 months

  4. Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ C30))

    Overall Quality of life ranging from 0-100 with 100 being best Quality of Life

    Measured: 42 months

  5. percentage subsequent treatment lines

    The percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of treatment.

    Measured: 42 months

  6. the reasons for forgoing subsequent treatment

    Reasons for forgoing subsequent treatment after progression on first-line treatment

    Measured: 42 months

Timeline

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

  1. First posted5 Dec 2018
  2. Study start1 May 2019
  3. Primary completion31 Jul 2025
  4. Study completion1 Dec 2026 (estimated)

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
Model description
phase 2 study
Masking
None (open label)
Enrolment
320 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03764553
Sponsor's protocol ID
2018_256
Acronym
LyRICX
Status last verified
Apr 2026
First submitted
29 Oct 2018
Last updated
21 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Liposomal Irinotecan, Carboplatin and Capecitabine in people with Esophageal Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 34 sites in Netherlands.

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 15 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Netherlands. 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?

This study is still under way. Results are not available in the source record yet.

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 (time frame: 42 months). The study lists 2 primary outcomes in all. 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 NCT03764553.

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 21 Aug 2026.

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LyRICX Clinical Trial NCT03764553 | AzTrials