NCT03764553

Brief 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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
320

participants targeted

Target at P75+ for phase_2

Timeline
2mo left

Started May 2019

Longer than P75 for phase_2

Geographic Reach
1 country

34 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress98%
May 2019Jul 2026

First Submitted

Initial submission to the registry

October 29, 2018

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 5, 2018

Completed
5 months until next milestone

Study Start

First participant enrolled

May 1, 2019

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2025

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2026

Expected
Last Updated

July 1, 2025

Status Verified

June 1, 2025

Enrollment Period

6.3 years

First QC Date

October 29, 2018

Last Update Submit

June 27, 2025

Conditions

Keywords

palliative chemotherapymetastatic esophagogastric cancerEfficacytoxicity

Outcome Measures

Primary Outcomes (2)

  • Progression free survival

    To compare the progression free survival

    42 months

  • Number of participants with treatment-related Neurotoxicity

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

    42 months

Secondary Outcomes (6)

  • Overall survival

    54 months

  • response rate

    42 months

  • adverse events

    42 months

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

    42 months

  • percentage subsequent treatment lines

    42 months

  • +1 more secondary outcomes

Other Outcomes (7)

  • Tumor micro environment

    54 months

  • Stromal markers in blood

    54 months

  • Growth velocity of patient derived tumor organoids

    54 months

  • +4 more other outcomes

Study Arms (3)

Liposomal irinotecan, leucovorin and 5FU

EXPERIMENTAL

IV 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

Drug: Liposomal IrinotecanDrug: 5-fluorouracilDrug: Leucovorin

Carboplatin and capecitabine

EXPERIMENTAL

IV 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

Drug: CarboplatinDrug: Capecitabine

oxaliplatin and capecitabine

EXPERIMENTAL

IV 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

Drug: CapecitabineDrug: Oxaliplatin

Interventions

Iv liposomal irinotecan

Liposomal irinotecan, leucovorin and 5FU

IV Carboplatin

Carboplatin and capecitabine

PO Capecitabine

Also known as: Xeloda
Carboplatin and capecitabineoxaliplatin and capecitabine

IV Oxaliplatin

oxaliplatin and capecitabine

IV 5-fluorouracil

Liposomal irinotecan, leucovorin and 5FU

IV Leucovorin

Liposomal irinotecan, leucovorin and 5FU

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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.

You may not qualify if:

  • 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.
  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (34)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Ziekenhuisgroep Twente

Almelo, Netherlands

Location

Flevoziekenhuis

Almere Stad, Netherlands

Location

Meander MC

Amersfoort, Netherlands

Location

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, 6815 AD, Netherlands

Location

Amphia Ziekenhuis

Breda, 4818 CK, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, 2625 AD, Netherlands

Location

Nij Smellinghe

Drachten, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

Catherina Ziekenhuis

Eindhoven, Netherlands

Location

Treant Zorggroep

Emmen, Netherlands

Location

Zuyderland Medisch Centrum

Geleen, Netherlands

Location

Admiraal de Ruijter Ziekenhuis

Goes, 4460 AA, Netherlands

Location

Sint Jansdal

Harderwijk, Netherlands

Location

Elkerliek ziekenhuis

Helmond, Netherlands

Location

Tergooi ziekenhuizen

Hilversum, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, Netherlands

Location

Treant zorggroep

Hoogeveen, 7909 AA, Netherlands

Location

Dijklander ziekenhuis

Hoorn, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Canisius Wilherlmina ziekenhuis

Nijmegen, Netherlands

Location

Radboud Universitair Medisch Centrum

Nijmegen, Netherlands

Location

VieCurie

Roermond, 6043 CV, Netherlands

Location

Laurentius Ziekenhuis

Roermond, Netherlands

Location

Bravis ziekenhuis locatie Roosendaal

Roosendaal, 4708 AE, Netherlands

Location

Ikazia ziekenhuis

Rotterdam, Netherlands

Location

Maasstadziekenhuis

Rotterdam, Netherlands

Location

Rivierenland Ziekenhuis

Rotterdam, Netherlands

Location

Haaglanden Medisch Centrum

The Hague, Netherlands

Location

UMCU

Utrecht, 3508 GA, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

irinotecan sucrosofateCarboplatinCapecitabineOxaliplatinFluorouracilLeucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • Jan M Prins, MD, PhD

    Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: phase 2 study
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

October 29, 2018

First Posted

December 5, 2018

Study Start

May 1, 2019

Primary Completion

July 31, 2025

Study Completion (Estimated)

July 1, 2026

Last Updated

July 1, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will not share

Locations