ClinicalTrials.gg
Active, not recruitingNCT03399071ICONICUpdated Feb 21, 2023

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

A Phase 2 interventional study of FLOT-A in Gastric Adenocarcinoma and Oesophageal Adenocarcinoma, sponsored by Royal Marsden NHS Foundation Trust. Active, not recruiting at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-21.

Sponsored by Royal Marsden NHS Foundation Trust · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled Jul 2017, registered Nov 2017).

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Phase
Phase 2
Study type
Interventional
Enrollment
44
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-14

Among 43 studies in Adenocarcinoma Of Esophagus with a site in United Kingdom — 10 open to participants now, 14 under way, 4 of them phase 3. Adenocarcinoma Of Esophagus · United Kingdom.

Enrollment
26th of 33
44 · median 259
Started
2017
the only one that year
Phase 2
8 of 43
none open now
Primary completion
2022-11
later than 0 of 13 live
Registered
20th of 43
by date
Lead sponsor
3 of 43
Royal Marsden NHS Foundation Trust

Among the 43 studies in Adenocarcinoma Of Esophagus with a site in United Kingdom, this one is the 26th largest by enrollment of the 33 interventional ones that give a count, is the only one that started in 2017, is one of 8 in phase 2, reaches primary completion later than 0 of the 13 other live ones, and was the 20th registered.

Adenocarcinoma Of Esophagus

354 studies on the registry are indexed under Adenocarcinoma Of Esophagus; 81 are open to participants now.

Browse Adenocarcinoma Of Esophagus studies →

Open to participants now

10 of the 43 studies in Adenocarcinoma Of Esophagus with a site in United Kingdom are open now. Recruiting first, the newest first:

5 more — sign in →

All 10 open studies →

A study can be open while its sites in United Kingdom have not opened yet or have stopped. Only those recruiting at a site in United Kingdom →

Who these studies take

Of the 70 Adenocarcinoma Of Esophagus studies recruiting now, 60 (86%) set no upper age limit and 2 (3%) stop at 75 or younger; 4 take children under 18; 3 take healthy volunteers.

This study: 18 Years and older · all sexes · no healthy volunteers.

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02

Study 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 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.

03

Conditions studied

  • Gastric Adenocarcinoma
  • Oesophageal Adenocarcinoma

Keywords

  • Gastric cancer
  • Oesophageal cancer
  • Gastro-oesophageal cancer
  • Perioperative
  • Immunotherapy
  • Anti PDL1
  • Avelumab
  • FLOT
04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Male/female patients aged ≥18 years
  2. confirmed gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (referred to as gastro-oesophageal adenocarcinoma (GOA) in this protocol).
  3. Oesophageal and gastric tumours should be TNM7 stage T1-4 and N0-N2, with no evidence of distant (M0) where the MDT believes that an R0 resection can be achieved after pre-operative chemotherapy.
  4. Absence of distant metastases on CT scan and PET scan and staging laparoscopy (where indicated) prior to study entry
  5. No prior therapy for GOA
  6. Considered fit for surgery by surgical/anaesthetic team
  7. Adequate bone marrow function:

    • (ANC) >1.5x10-9/L
    • White blood count >3x10-9/L
    • ≥100x10-9/L
    • (Hb) >9g/dL (can be post-transfusion)
  8. Adequate renal function: 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.
  9. Adequate liver function

    • Serum \<22 umol/L
    • /AST ≤2.5x
  10. Adequate coagulation profile

    • (INR) \< 1.5
    • Activated Prothrombin Time (APTT) \< 1.5xULN
  11. Patients on oral anticoagulation are advised to change to low molecular weight heparin prior to study entry, to be eligible
  12. performance status 0 or 1
  13. (BMI) ≤30
  14. 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 document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment.
  15. Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans

Exclusion criteria

Exclusion Criteria

Patients are not eligible for the trial if any of the exclusion criteria below are met:

  1. Any or known reaction to any of the study drugs, or components of Folinic acid, Oxaliplatin, 5FU or Docetaxel
  2. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 v 4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma)
  3. If known dihydropyrimidine dehydrogenase (DPD) deficiency, patients must be deemed safe to receive appropriate dose-adjusted 5-FU according to the identified mutation.
  4. Patients who have received , 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
  5. Prior 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.
  6. Patients recommended to have radiotherapy as part of routine management for their GOA are ineligible
  7. Any immunodeficiency disorder
  8. Any active disease that has required systemic treatment in the past 2 years (i.e, with use of disease modifying agents, or 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
  9. Prior organ transplantation, including stem-cell transplantation
  10. History of inflammatory bowel disease with the following exception:

    • Patients with a history of ulcerative colitis who have had a colectomy are eligible
  11. Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis
  12. Cerebrovascular disease (including (TIA) and strokes) within the previous year
  13. 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 ( Classification Class II or above)
  14. Other severe acute or chronic medical conditions or psychiatric conditions including recent (within the past year) active suicidal ideation or behaviour
  15. 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.
  16. Major surgery, major trauma or open within 28 days prior to registration (not including staging laparoscopy)
  17. Evidence of bleeding diathesis or coagulopathy
  18. Active infection requiring systemic therapy, non-healing wound, ulcer or bone fracture requiring therapy
  19. Known positive tests for (HIV) infection
  20. 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.
  21. Known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
  22. Use of within 28 days of initiation of study therapy, or anticipation that a live attenuated vaccine will be required during the study
  23. 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 or must agree to use highly effective . 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.
  24. Any patient specific factors which are likely to interfere with compliance of trial specific procedures or treatment.
Terms in these criteria, in plain language(29)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
44 participants (actual)

Study arms

  • Experimental
    FLOT plus Avelumab (FLOT-A)

    Avelumab 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

    Drug: FLOT-A

Interventions

  • DrugFLOT-A

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

06

What researchers measure

Primary outcomes

  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.

    Time frame: Within 2 years of study opening

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: Within 5 years

07

Study locations

1 site
08

References and documents

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 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jul 2017 to primary completion in Nov 2022, 63 months.

Of 51 non-industry phase 2 interventional studies under Adenocarcinoma Of Esophagus, half reached primary completion within 61 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 82. This study's 63 months is close to that.

Counting every sponsor, half of 60 studies reached it within 55 months; a quarter within 41 and three quarters within 80.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 16, 2017
First posted
Jan 16, 2018
StartActual
Jul 31, 2017
Primary completionActual
Nov 1, 2022
CompletionEst.
Aug 15, 2025
Last update
Feb 21, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 21, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03399071
Responsible party
Sponsor
First posted
Jan 16, 2018
Start date
Jul 31, 2017
Primary completion
Nov 1, 2022
Completion
Aug 15, 2025 (estimated)
Last update
Feb 21, 2023

Study contacts

Marco Gerlinger, MD, FRCP
principal investigator · The Royal Marsden NHSFT

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Feb 2023. You cannot join it, but the record below documents what was studied.

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