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Adenocarcinoma of the EsophagusPhase 1/2ARTEMIS-EsoNCT03307941

Assessment of Metabolic & Path Response w/ RCT & ImT Before Surgery in Locally Advanced Esoph and Gastro-esoph Jction CA

A Phase 1/2 study testing Monalizumab, Oxaliplatin and 5-Fluorouracil in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Jules Bordet Institute at 1 site in Belgium.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

ARTemIS-Eso is a phase I-II, three-level, open-label trial with a dose-expansion cohort at recommended schedule in both esophageal cancer histological groups (squamous cell carcinoma and adenocarcinoma) of RCT and ImT administered prior to surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Monalizumab, Oxaliplatin and 5-Fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteBelgium
Study dates
20 Jul 2017to 11 Dec 2017
Phase
Phase 1/2
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

  • Age ≥ 18 years old
  • ECOG performance status ≤ 1
  • Female and Male
  • Must have histologically confirmed esophageal ADC or SCC or gastro-esophageal junction ADC (Siewert I and II) eligible for a curative intent resection (recommended exploration by EUS and diagnostic laparoscopy in gastro-esophageal junctions) without restriction in age and sex and candidate for neoadjuvant RCT.
  • At least classified clinical T3Nx or any T, N+ according to cTNM version 7.
  • Negative serum pregnancy test (for women of childbearing potential) within 7 (+/-1) days prior to the beginning of treatment.
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  • Women of childbearing potential must agree to use one highly effective method of contraception at study entry (if this is not already the case, put in place within 1 week after ICF signature, and at the very latest before 1st administration of study treatment), during the study treatment administration and at least 5 months after the last administration of study treatment.
  • Men must agree to use condom during the course of this study and for at least 5 months after the last administration of the study treatment.
  • Adequate bone marrow function as defined below:
  • Absolute neutrophil count ≥1500/µL or 1.5x109/L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥100000/µL or 100x109/L
  • Adequate liver function as defined below:
  • Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome < 3xUNL is allowed
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN
  • Adequate renal function as defined:
  • Creatinine ≤ 1.5 x UNL or creatinine clearance >60 mL/min
  • Participants must have normal cardiac and pulmonary functions defined with ultrasonography (LVEF>50%) and pulmonary function tests (including DLCO (diffusing capacity factor of the lung for carbon monoxide)).
  • Completion of all necessary screening procedures within 28 days prior to enrolment.
  • Accessible tumour for biopsies through upper gastro-intestinal endoscopy (for translational research activities).
  • Signed Informed Consent form (ICF) obtained prior to any study related procedure and study treatment.
  • For the phase II expansion cohort only, significant FDG uptake at the primary tumour on baseline PET/CT, performed not more than 7 days before the beginning of the first course of CT, defined as SUVmax > 2x the mean liver uptake.

Who cannot join

  • Subjects meeting one of the following criteria are not eligible for this study:
  • Patient ineligible for curative intent surgery:
  • T4 with involvement of mediastinal structures as tracheobronchial, recurrent nerve, aorta over 90° of its circumference, vertebral body
  • Tumour ≥ 4cm in diameter developed above the carina
  • Visceral metastasis
  • Metastatic lymph nodes: supraclavicular and/or lombo-aortic
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  • Cervical esophageal cancer defined as a tumor involving the lower border of the cricoid cartilage (at the level of the sixth cervical vertebra) to the thoracic inlet 5cm down under, generally between 18 and 20 cm from the dental arcade
  • Uncontrolled concurrent illness or any significant disease that, in the investigator's opinion, would exclude the patient from the study.
  • Absolute contraindication for surgery: respiratory failure (VEMS < 1000mL), weight loss> 20%, renal failure: creatinine > 1.5 ULN, myocardial infarct < 6 months, evolutive cardiopathy, ECOG 3 and 4, non-compensated cirrhosis.
  • Pregnant and/or lactating women.
  • Uncontrolled diabetes.
  • Individuals with a history of a different malignancy within the last 5 years are ineligible except cervical cancer in situ, and early stage basal cell or squamous cell carcinoma of the skin.
  • Patients with active, known or suspected autoimmune disease or condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive systemic treatment.
  • (Exception: patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring immunosuppressive systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to be enrolled.
  • Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active/autoimmune disease.
  • Patients with diseases known for hypersensitivity to radiotherapy.
  • Prior treatment for esophageal cancer: surgery, radiotherapy, chemotherapy or immunotherapy (in particular but not limited to anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumour vaccines or other immuno-stimulatory anti-tumour agents.
  • Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (ribonucleic acid or HCV antibody) indicating acute or chronic infection.
  • Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of allergy to study drug components or excipients.
  • Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Institut Jules Bordet

    Brussels, 1000

Other trials in Belgium

About this study

Official title: Assessment of Metabolic and Pathological Response to Treatment With RCT and ImT Before Surgery in Locally Advanced Esophageal and Gastro-esophageal Junction Cancer: ARTemIS-Eso, a Three-level, Open-label, Phase I-II Study

ARTemIS-Eso is a phase I-II, three-level, open-label trial with a dose-expansion cohort at recommended schedule in both esophageal cancer histological groups (squamous cell carcinoma and adenocarcinoma) of RCT and ImT administered prior to surgery.

Read the detailed description

This study is indicated to patients with adenocarcinomas of the esophagus or gastro-esophageal junction and squamous cell carcinoma of the esophagus.

The study consists of 2 parts:

Phase I of the study is composed of the 3 following levels, corresponding to changes in the schedule and the number of administrations of monalizumab:

Level 1: monalizumab (ImT) administration starts 2 weeks after the end of RCT (Total of 3 ImT doses). A maximum of 7 days delay is allowed.

Level 2: monalizumab administration starts directly at the end of RCT (Total of 4 ImT doses). The first dose of monalizumab should be given on the following working day after the last radiotherapy administration.

Level 3: monalizumab administration starts 2 weeks after the start of RCT (total of 6 ImT doses). A maximum of 7 days delay is allowed.

Phase II (Expansion cohort): At the recommended level determined in phase I and according to the number of patients already accrued, approximately 48-51 additional patients (half-SCC and half-ADC) are included with the aim of assessing the activity of the recommended combination.

Being tested
Monalizumab, Oxaliplatin, 5-Fluorouracil, Metabolic, Surgery
Medical subject headings
Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma

What participants receive

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

  • MonalizumabDrug

    Also called IPH2201

    Monalizumab (IPH2201) is given at the recommended dose of 10 mg/kg, intravenously (infusion during 60 minutes) every two weeks

  • OxaliplatinDrug

    A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level

  • 5-FluorouracilDrug

    A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level

  • MetabolicRadiation

    Radiation therapy must start the first day of FOLFOX chemotherapy. Radiation is given once daily for 5 consecutive days; on the days that the patient receives chemotherapy (and monalizumab when applicable), chemotherapy (and monalizumab) should be given prior to radiotherapy.

  • MetabolicOther

    Also called FDG-PET

    18-FDG-PET scan will be performed just before the beginning of radio-chemotherapy (D10-D14) and will be blinded for investigators and patients. Another 18-FDG-PET will be performed before surgery (surgery Day-5 to surgery Day -1) to exclude metastatic evolution

  • SurgeryProcedure or surgery

    Surgery is performed preferably 8 weeks after the completion of the radio-chemotherapy, and it should not be performed less than one week after the last dose of monalizumab

Study groups in NCT03307941
Study groupRoleWhat they receive
Single arm (classic 3+3 design)OtherNot described
Receives: Drug: Monalizumab; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Radiation: Metabolic; Other: Metabolic; Procedure: Surgery

What is being measured

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

  1. Phase I: determine the feasibility to administer monalizumab

    Successful and safe administration of the combination of radio-chemotherapy and at least 2 doses of immunotherapy

    Measured: From date of randomization until the date of first documented disease recurrence, assessed up to 28 months

  2. Phase II: pCR rate

    Defined by the absence of any tumoral cells on the surgical specimen post esophagectomy

    Measured: At date of surgery, assessed at 16 weeks post randomization

Secondary outcomes (7)

  1. Phase I: pCR rate

    Defined by the absence of any tumoral cells on the surgical specimen post esophagectomy

    Measured: At date of surgery, assessed at 16 weeks post randomization

  2. Phase I: DFS and OS at 2 years after surgery

    DFS and OS at 2 years after surgery

    Measured: From date of randomization until the date of first documented event, assessed up to 28 months

  3. Phase I: Human Anti-Human Antibodies against monalizumab (HAHA) in serum

    Human Anti-Human Antibodies against monalizumab (HAHA) in serum

    Measured: Week 5 to 3 months post surgery

  4. Phase II: Two year-disease free survival (DFS) and two year-overall survival (OS)

    Two year-disease free survival (DFS) and two year-overall survival (OS)

    Measured: 2 years after the date the last patient had his surgery provided the trial objectives have been met

  5. Phase II: Toxicity profile according to CTCAE v.4.03

    Toxicity profile according to CTCAE v.4.03

    Measured: From date of randomization until the date of first documented event, assessed up to 28 months

  6. Phase II: Metabolic response after 1 course of CT and before surgery

    Metabolic response after 1 course of CT and before surgery

    Measured: from week 1 up to the time of surgery

  7. Phase II: Number of the tumour-infiltrating lymphocytes (TILs)

    Number of the tumour-infiltrating lymphocytes (TILs)

    Measured: at baseline, after 1 course of CT at week 3 and after surgery at 16 weeks

Timeline

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

  1. First posted12 Oct 2017
  2. Study start20 Jul 2017
  3. Primary completion11 Dec 2017
  4. Study completion11 Dec 2017

Why it stopped: Suspended collaboration with the company providing the study drug

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03307941
Sponsor's protocol ID
IJB-GASTON-002-ARTEMIS-Eso
Other IDs
2016-000935-42, 2016
Acronym
ARTEMIS-Eso
Status last verified
Dec 2017
First submitted
27 Oct 2016
Last updated
19 Dec 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Monalizumab, Oxaliplatin and 5-Fluorouracil in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Jules Bordet Institute at 1 site in Belgium.

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 23 inclusion and 21 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: withdrawn, as of the sponsor's last update on 19 Dec 2017. 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 Belgium. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 was withdrawn before enrolling participants, so there are no results.

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?

Phase I: determine the feasibility to administer monalizumab (time frame: From date of randomization until the date of first documented disease recurrence, assessed up to 28 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 NCT03307941.

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 19 Dec 2017.

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