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Gastric AdenocarcinomaPhase 2ICONICNCT03399071

Study Title: Peri-operative Immuno-Chemotherapy in Operable Oesophageal and Gastric Cancer

A Phase 2 study testing FLOT-A in people with Gastric Adenocarcinoma and Oesophageal Adenocarcinoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

A single centre phase II trial of peri-operative chemo-immunotherapy in operable gastro-oesophageal adenocarcinoma (GOA). This trial is designed to evaluate the safety and efficacy of administering Avelumab, an anti-PD-L1 monoclonal antibody, with cytotoxic FLOT chemotherapy for patients with operable GOA treated… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
FLOT-A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited Kingdom
Study dates
31 Jul 2017to 15 Aug 2025
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

  • Male/female patients aged ≥18 years
  • Histologically confirmed gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (referred to as gastro-oesophageal adenocarcinoma (GOA) in this protocol).
  • Oesophageal and gastric tumours should be TNM7 stage T1-4 and N0-N2, with no evidence of distant metastases (M0) where the MDT believes that an R0 resection can be achieved after pre-operative chemotherapy.
  • Absence of distant metastases on CT scan and PET scan and staging laparoscopy (where indicated) prior to study entry
  • No prior therapy for GOA
  • Considered fit for surgery by surgical/anaesthetic team
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  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) >1.5x10-9/L
  • White blood count >3x10-9/L
  • Platelets ≥100x10-9/L
  • Haemoglobin (Hb) >9g/dL (can be post-transfusion)
  • Adequate renal function: Creatinine Clearance of >50ml/min or measured EDTA Clearance of ≥50ml/min. If the calculated Creatinine Clearance is <60ml/min then a measured EDTA Clearance is required. If available, the EDTA Clearance should always take precedence over the Creatinine Clearance.
  • Adequate liver function
  • Serum bilirubin <22 umol/L
  • ALT/AST ≤2.5x ULN
  • Adequate coagulation profile
  • International Normalised Ratio (INR) < 1.5
  • Activated Prothrombin Time (APTT) < 1.5xULN
  • Patients on oral anticoagulation are advised to change to low molecular weight heparin prior to study entry, to be eligible
  • ECOG performance status 0 or 1
  • Body Mass Index (BMI) ≤30
  • Patient is fit to undergo all protocol investigations and receive all protocol treatment based on the assessment in the surgical and oncology clinics. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment.
  • Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans

Who cannot join

  • Patients are not eligible for the trial if any of the exclusion criteria below are met:
  • Any contraindication or known hypersensitivity reaction to any of the study drugs, or components of Folinic acid, Oxaliplatin, 5FU or Docetaxel
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma)
  • If known dihydropyrimidine dehydrogenase (DPD) deficiency, patients must be deemed safe to receive appropriate dose-adjusted 5-FU according to the identified mutation.
  • Patients who have received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
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  • Patients recommended to have radiotherapy as part of routine management for their GOA are ineligible
  • Any immunodeficiency disorder
  • Any active autoimmune disease that has required systemic treatment in the past 2 years (i.e, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or is expected to deteriorate when receiving avelumab, with the following exceptions:
  • Patients only receiving hormone replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy (doses ≤10mg - or equivalent - of prednisolone per day) for adrenal or pituitary insufficiency) are eligible.
  • Patients with vitiligo or psoriasis not requiring immunosuppressive treatment are eligible
  • Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement
  • Administration of steroids through a route known to result in minimal systemic exposure (topical, intranasal intra-ocular, or inhalation) are acceptable. Steroids as pre-medication for hypersensitivity reactions e.g. CT contrast are also acceptable
  • Prior organ transplantation, including allogeneic stem-cell transplantation
  • History of inflammatory bowel disease with the following exception:
  • Patients with a history of ulcerative colitis who have had a colectomy are eligible
  • Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis
  • Cerebrovascular disease (including transient ischaemic attacks (TIA) and strokes) within the previous year
  • Cardiovascular diseases as follows:
  • Myocardial infarction within the previous year
  • Serious cardiac arrhythmia requiring medication (for example, ventricular tachycardia, supraventricular tachycardia or atrial fibrillation with a resting heart rate > 110bpm)
  • Unstable angina
  • Congestive cardiac arrhythmia (New York Heart Association Classification Class II or above)
  • Other severe acute or chronic medical conditions or psychiatric conditions including recent (within the past year) active suicidal ideation or behaviour
  • Current signs or symptoms of any other severe progressive or uncontrolled hepatic, haematologic, gastrointestinal, endocrine, respiratory or cardiac disease other than directly related to gastrooesophageal adenocarcinoma, which in the opinion of the investigator,might impair the subject's tolerance of trial treatment or procedures.
  • Major surgery, major trauma or open biopsy within 28 days prior to registration (not including staging laparoscopy)
  • Evidence of bleeding diathesis or coagulopathy
  • Active infection requiring systemic therapy, non-healing wound, ulcer or bone fracture requiring therapy
  • Known positive tests for human immunodeficiency virus (HIV) infection
  • Active Hepatitis A, B or C infection. If there is a previous history of Hepatitis infection which has been treated and cleared, there must be evidence that disease is not currently active.
  • Known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
  • Use of live attenuated vaccine within 28 days of initiation of study therapy, or anticipation that a live attenuated vaccine will be required during the study
  • Pregnancy/of child bearing potential. Pregnancy must be excluded with a negative serum pregnancy test, within 7 days before initiation of therapy, if the risk of conception exists. Sexually active female patients must be surgically sterile or be postmenopausal or must agree to use highly effective contraception. Sexually active male patients must be surgically sterile or must agree to use highly effective contraception, i.e. methods with a failure rate of <1% per year (see section 5.4 for full definition and examples of highly effective contraception). Lactation- breast-feeding is contraindicated and must be discontinued for the duration of the trial and for at least 1 month afterward the last dose of Avelumab.
  • Any patient specific factors which are likely to interfere with compliance of trial specific procedures or treatment.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • The Royal Marsden Hospital

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: Study Title: Peri-operative Immuno-Chemotherapy in Operable Oesophageal and Gastric Cancer (ICONIC Trial)

A single centre phase II trial of peri-operative chemo-immunotherapy in operable gastro-oesophageal adenocarcinoma (GOA). This trial is designed to evaluate the safety and efficacy of administering Avelumab, an anti-PD-L1 monoclonal antibody, with cytotoxic FLOT chemotherapy for patients with operable GOA treated according to a peri-operative protocol.

This trial is in 2 stages: the first stage will establish the safe and tolerated maximum administered dose (MAD) of Avelumab in combination with FLOT and the second stage will assess the efficacy of this combination therapy in achieving pathological complete response (pCR) and peri-operative safety.

Read the detailed description

Patients will receive chemo-immunotherapy consisting of FLOT chemotherapy (Folinic acid 200mg/m2 iv infusion day 1, Oxaliplatin 85mg/m2 iv infusion day 1, Docetaxel 50mg/m2 iv day 1, Fluorouracil 2600mg/m2 over 24 hours iv) and the PD-L1 inhibiting monoclonal antibody Avelumab. The safe dose of Avelumab in combination with FLOT will be established in a safety run-in phase with a standard 3+3 design, starting with the recommended dose of 10mg/kg iv Avelumab (dose level 0) in which a dose reduction to 7mg/kg iv (dose level -1) may occur. Four cycles of two-weekly chemo-immunotherapy will be administered before surgery and four further cycles post-operatively in patients who are fit enough to receive further chemo-immunotherapy after surgery. Resectional surgery will take place 4-8 weeks following the last dose of chemo-immunotherapy in patients who remain fit.

Study Objectives:

To evaluate the safety, efficacy and toxicities and to explore biomarkers of peri-operative chemo-immunotherapy with Avelumab and FLOT.

Being tested
FLOT-A
Keywords
Gastric cancer, Oesophageal cancer, Gastro-oesophageal cancer, Perioperative, Immunotherapy, Anti PDL1, Avelumab, FLOT
Medical subject headings
Adenocarcinoma Of Esophagus, Stomach Neoplasms, Esophageal Neoplasms

What participants receive

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

  • FLOT-ADrug

    This is a single-arm study with all patients receiving combination FLOT-A

Study groups in NCT03399071
Study groupRoleWhat they receive
FLOT plus Avelumab (FLOT-A)ExperimentalAvelumab 10mg/kg (or Maximum Administered Dose established in safety run-in) iv infusion over 1 hour. Followed by FLOT: Oxaliplatin 85mg/m2 iv infusion day 1 over 2 hours, Folinic acid 200mg/m2 iv infusion day 1 over 2 hours, Docetaxel 50mg/m2 iv day 1 over 1 hour, Fluorouracil 2600mg/m2 over 24 hours iv
Receives: Drug: FLOT-A

What is being measured

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

  1. Pathological complete response rate of combination FLOT-A

    The primary objective is to assess the efficacy of FLOT-A in the peri-operative setting in patients with operable GOAs. We aim to increase the pCR rate after peri-operative treatment from 10% (minimum expected path CR rate for peri-operative FLOT chemotherapy), to a superior pCR rate of >25%, by adding Avelumab to FLOT.

    Complete histopathologic response is defined by no vital tumour cells neither in the oesophagus, the stomach nor in the regional lymph nodes. In cases of residual tumour, the response assessment will follow criteria described by Mandard et al.

    Measured: Within 2 years of study opening

Secondary outcomes (4)

  1. Number of participants with grade 3 or 4 treatment-related adverse events as assessed by CTCAE v4.0

    Safety of peri-operative FLOT-A will be assessed by summarising grade 3-4 toxicity and DLT rates as proportions.

    Measured: Within 2 years

  2. Radiological response rate using RECIST 1.1 criteria

    Radiological response rate assessed at the pre-operative scan using RECIST 1.1 criteria. Radiological tumour response before surgery will be defined as partial response or complete response.

    Measured: Within 3 years

  3. Median progression free survival by Kaplan Meir method

    PFS will be summarised using Kaplan Meier methods, presenting median survival with 95% confidence intervals. PFS is defined as time from registration to clinical/radiological progression or death from any cause. Patients event free at time of analysis will be censored at last follow-up date.

    Measured: Within 5 years

  4. Median overall survival by Kaplan Meir method

    OS will be summarised using Kaplan Meier method, presenting median survival with 95% confidence intervals. OS is defined as time from registration to date of death of any cause. Patients event free at time of analysis will be censored at last follow-up date.

    Measured: Within 5 years

Timeline

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

  1. First posted16 Jan 2018
  2. Study start31 Jul 2017
  3. Primary completion1 Nov 2022
  4. Study completion15 Aug 2025 (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
Model description
All patients will receive chemo-immunotherapy consisting of FLOT chemotherapy and the PD-L1 inhibiting monoclonal antibody Avelumab. Four cycles of two-weekly chemo-immunotherapy will be administered before surgery and four further cycles post-operatively in patients who are fit enough to receive further chemo-immunotherapy after surgery. Resectional surgery will take place 4-8 weeks following the last dose of chemo-immunotherapy in patients who remain fit.
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03399071
Sponsor's protocol ID
4557
Acronym
ICONIC
Status last verified
Feb 2023
First submitted
16 Nov 2017
Last updated
21 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

    PubMed 35623069

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FLOT-A in people with Gastric Adenocarcinoma and Oesophageal Adenocarcinoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

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 34 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: status not confirmed, as of the sponsor's last update on 21 Feb 2023. 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 United Kingdom. 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?

Results are not available in the source record.

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?

Pathological complete response rate of combination FLOT-A (time frame: Within 2 years of study opening). 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 NCT03399071, which also lists 1 linked publication.

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 Feb 2023.

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