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Gastric AdenocarcinomaPhase 2AuspiCiOusNCT05177133

Anti-PD-1 and CapOx for the First-line Treatment of dMMR Esophagogastric Cancer (AuspiCiOus)

A Phase 2 study testing Capecitabine, Oxaliplatin and Retifanlimab in people with Gastric Adenocarcinoma and Esophageal Adenocarcinoma, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 8 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

To investigate the effects of the combination of two chemotherapies followed by immunostimulants on the interferon gamma expression and infiltration of cytotoxic T cells in the tumour microenvironment in patients with previously untreated metastatic or locally advanced esophagogastric cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Capecitabine, Oxaliplatin and Retifanlimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
8 sitesNetherlands
Study dates
5 Nov 2021to 4 Nov 2029
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 ICH/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 HER2 negative adenocarcinoma of the stomach or gastroesophageal junction (Siewert II and III); 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
  • dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2 en MSH6
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  • Primary tumor or metastasis accessible for repeat fresh histological biopsies
  • 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 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 pregnancy test (urine or serum; beta-human chorionic gonadotropin (β-hCG)) documented 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

  • Severe renal impairment (CLcr ≤ 30 ml/min)
  • Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment.
  • Any prior anti-cancer chemotherapy, biologic or investigational therapy for metastatic or irresectable stomach or oesophageal cancer
  • Disease progression within six months after completion of (neo)adjuvant chemotherapy containing a fluoropyrimidine and/or platinum compound. (Disease progression within 6 months after completion of neoadjuvant chemoradiation carboplatin AUC 2 and paclitaxel 50 mg/m2 is allowed.)
  • All target lesions in a radiation field without documented disease progression.
  • 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).
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  • Past or current malignancy other than entry diagnosis interfering with prognosis of metastatic gastroesophageal cancer.
  • Known uncontrollable hypersensitivity or contraindications to any of the components of retifanlimab, fluoropyrimidines, leucovorin, oxaliplatin. 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)
  • Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • 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 of the current study.
  • Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol.
  • 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 DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.
  • Pre-existing motor or sensory neurotoxicity greater than CTCAE grade 1.
  • History of organ transplant, including allogeneic stem cell transplantation.
  • Receiving probiotics as of the first dose of study treatment.

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Joris Bos, MSc contact

0204440506

j.bos3@amsterdamumc.nl

8 sites in 1 country

Netherlands8 sites, 8 recruiting

  • Academic Medical Center, Medical Oncology

    Amsterdam, 1100 DD

    H WM van Laarhoven, MD, PhD, PhD, 31205665955, h.vanlaarhoven@amsterdamumc.nl

    Hanneke WM van Laarhoven, MD, PhD, PhD

    Recruiting

  • Amsterdam UMC, location VUmc

    Amsterdam

    H WM van Laarhoven, h.vanlaarhoven@amsterdamumc.nl

    S Derks, s.derks@amsterdamumc.nl

    Recruiting

  • Catharina ziekenhuis

    Eindhoven

    G J Creemers, Jan.creemers@catharinaziekenhuis.nl

    Recruiting

  • Medisch Centrum Leeuwarden

    Leeuwarden

    E Fiets, Edward.Fiets@mcl.nl

    Not yet recruiting

  • LUMC

    Leiden

    M Slingerland, m.slingerland@lumc.nl

    Not yet recruiting

  • Radboud UMC

    Nijmegen

    H Westdorp, mailto:Harm.Westdorp@radboudumc.nl

    Recruiting

  • Erasmus MC

    Rotterdam

    B Mostert, b.mostert@erasmusmc.nl

    Not yet recruiting

  • UMC Utrecht

    Utrecht

    N Haj Mohammad, n.hajmohammad@umcutrecht.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Anti-PD-1, Capecitabine, and Oxaliplatin for the First-line Treatment of dMMR Esophagogastric Cancer (AuspiCiOus-dMMR): a Proof-of-principle Study

To investigate the effects of the combination of two chemotherapies followed by immunostimulants on the interferon gamma expression and infiltration of cytotoxic T cells in the tumour microenvironment in patients with previously untreated metastatic or locally advanced esophagogastric cancer.

Read the detailed description

This is a multi-center, open label, proof-of-principle study for patients with previously untreated metastatic or locally advanced esophagogastric cancer. Patients are sequentially treated with standard of care capecitabine and oxaliplatin, and retifanlimab. Patients are treated with 2 cycles of CapOx (1 cycle is 3 weeks) and sequentially with 4-weekly cycles of retifanlimab up to 2 years. The investigators will include 25 patients in this study.

Biopsies, blood and faeces will be collected during treatment for assessment of infiltrating immune cells and IFNy expression, as well as for other translational research purposes. CT scans are made for evaluation of tumor response before and after chemotherapy, and after 2-3 cycles of immunotherapy.

Being tested
Capecitabine, Oxaliplatin, Retifanlimab
Keywords
Advanced esophagogastric cancer, Infiltrating immune cells, IFNy expression, chemotherapy, immunotherapy, Microsatellite instability
Medical subject headings
Adenocarcinoma Of Esophagus, Microsatellite Instability

What participants receive

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

  • CapecitabineDrug

    Also called Xeloda

    PO Capecitabine

  • OxaliplatinDrug

    Also called Oxaliplatin Accord

    IV Oxaliplatin

  • RetifanlimabDrug

    Also called INCMGA00012

    IV retifanlimab

Study groups in NCT05177133
Study groupRoleWhat they receive
Capecitabine, oxaliplatin and retifanlimabExperimentalIV and PO Capecitabine 1000 mg/m2, oxaliplatin 130 mg/m2, every three weeks (up to 2 cycles) IV retifanlimab 500mg, every four weeks
Receives: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Retifanlimab

What is being measured

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

  1. Effect of chemo- and immunotherapy on the interferon gamma expression signature in the tumor microenviornment

    RNA expression analysis (Nanostring) to determine changes in Interferon gamma expression signature before and during treatment

    Measured: 40 months

  2. Effect of chemo- and immunotherapy on the immune infiltrate in the tumor microenvironment

    Flow cytometry to determine changes in immune infiltrate in the tumor before and during treatment

    Measured: 40 months

  3. Effect of chemo- and immunotherapy on the immune infiltrate on the tumor microenvironment

    Multicolor immunohistochemstry to determine changes in immune infiltrate in the tumor before and during treatment

    Measured: 40 months

Secondary outcomes (8)

  1. Overall survival

    Determine overall survival of patients within the study

    Measured: 60 months

  2. Overall survival

    Compare overall survival with a propensity score matched cohort

    Measured: 60 months

  3. Progression free survival (PFS)

    Assess the PFS of patients within the study

    Measured: 60 months

  4. Progression free survival (PFS)

    Compare PFS with a propensity score matched cohort

    Measured: 60 months

  5. Response rate

    Determine response rate by comparing RECIST evaluation of CT scans before and during treatment

    Measured: 60 months

  6. Adverse events

    To determine adverse events of CapOx and retifanlimab

    Measured: 60 months

  7. Measure PROMs via established PROFILES

    Patient reported outcome measures (PROMs) are measured with the established PROFILES infrastructure (Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship). PROMs will be assessed and compared at baseline and throughout treatment

    Measured: 60 months

  8. Percentage subsequent treatment lines

    The percentage of patients proceeding to subsequent lines of treatment after progression

    Measured: 60 months

Timeline

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

  1. First posted4 Jan 2022
  2. Study start5 Nov 2021
  3. Primary completion1 May 2025 (estimated)
  4. Study completion4 Nov 2029 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05177133
Sponsor's protocol ID
NL77094.018.21
Acronym
AuspiCiOus
Status last verified
Aug 2024
First submitted
7 Sep 2021
Last updated
2 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Capecitabine, Oxaliplatin and Retifanlimab in people with Gastric Adenocarcinoma and Esophageal Adenocarcinoma, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 8 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 17 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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?

Contact Joris Bos, MSc (0204440506, j.bos3@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of chemo- and immunotherapy on the interferon gamma expression signature in the tumor microenviornment (time frame: 40 months). The study lists 3 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 NCT05177133.

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 2 Aug 2024.

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