Condition category
Cancer
Date applied
10/09/2013
Date assigned
10/09/2013
Last edited
13/05/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Mr Ian Emerson

ORCID ID

Contact details

Christie Hospital NHS Foundation Trust
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom
-
Ian.emerson@christie.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

14133

Study information

Scientific title

A Phase II Trial to Assess the Activity of NY-ES-O1 Targeted T Cells in Advanced Oesophagogastric Cancer

Acronym

ATTACK-OG

Study hypothesis

This is a trial of adoptive T cell therapy using autologous T cells genetically engineered to target the tumour associated antigen NY-ESO-1. Eligible patients will undergo leukapheresis to retrieve sufficient T cells which will be gene modified and expanded in the laboratory. Patients will undergo preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by
fludarabine (25mg/m2) day -5 to day -1. The NY-ESO-1 gene modified cells will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous IL2 (100000 U/kg) from day 0 to day 4.

Primary Objective:
To explore the activity of adoptive cell therapy targeted to NY-ESO-1 in oesophagogastric cancer patients who are NY-ESO-1 and HLA-A*0201 positive.

Secondary Objectives:
1. Evaluation of feasibility and tolerability of adoptive cell therapy
targeted to NY-ESO-1 in oesophagogastric cancer patients who are
NY-ESO-1 positive and HLA-A*0201 positive.
2. Evaluation of progression free survival.
3. Evaluation of the duration of response.
4. Assessment of overall survival.

Exploratory Objectives:
1. Laboratory analysis of gene modified T-cell survival and other
immunological assessments.
2. Evaluation of response rate by immune related Response Criteria
(irRC).
3. Evaluation of tumour marker responses.
4. Assessment of the cost of treatment.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=14133

Ethics approval

13/SS/0041

Study design

Phase II open-label non-randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Oesophagus, Stomach

Intervention

Interluekin 2, Patients will receive up to 12 doses of intravenous IL-2 (100000 U/kg) from day 0 to day 4
NY-ESO-1 T-cells, The NY-ESO-1 gene modified cells will be re-infused on day 0 Preconditioning chemotherapy, cyclophosphamide (60 mg/kg) day -7 and day -6
Preconditioning chemotherapy, fludarabine (25 mg/m2) day -5 to day -1

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

Response rate according to RECIST 1.1; Timepoint(s): Week 6 post treatment, week 12 post treatment, and then 12 weekly until patient off study

Secondary outcome measures

Not provided at time of registration

Overall trial start date

01/09/2013

Overall trial end date

01/05/2018

Reason abandoned

Eligibility

Participant inclusion criteria

Prescreening:
1. Patients must be HLA-A0201 positive on pre-screen blood test
2. If confirmed HLA-A0201 positive, subjects tumour sample must stain positive by immunohistochemistry for NYES-O1 and/or LAGE (either diagnostic or more recent biopsy is acceptable. Subject may require additional biopsy if insufficient tumour material available form diagnostic sample).

Main Study:
1. Patients must have histologically confirmed oesophagogastric cancer and have received prior chemotherapy.
2. There must be measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
3. Patients may have had any previous systemic therapies provided they are otherwise fit for treatment
4. Age equal to or greater than 18 years
5. World Health Organisation (WHO) performance status of 0 or 1
6. Patients must be human leukocyte antigen (HLA-A2) positive
7. Their tumour must stain positive by immunohistochemistry for NY-ESO-1 and/or LAGE (either diagnostic or more recent biopsy is acceptable)
8. Life expectancy >3months
9. Left ventricular ejection fraction (LVEF) > 50% as measured by ECHO or Multi Gated Acquisition (MUGA) and satisfactory stress ECHO (if over 60 or had previous cardiotoxic therapy)
10. Haematological and biochemical indices:
10.1. Haemoglobin (Hb) ≥ 8.0 g/dL
10.2. Neutrophils ≥ 1.0 x 109/L
10.3. Platelets (Plts) ≥ 100 x 109/L
11. Any of the following abnormal baseline liver function tests:
11.1. Serum bilirubin 1.5 x ULN
11.2. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3 x ULN unless patient has liver metastases when can be < 5 x ULN
11.3. Serum creatinine ≤ 150 μmol/L or creatinine clearance > 50 ml/min
These measurements must be performed prior to leukapheresis and again prior to commencing preconditioning chemotherapy.
12. The chemotherapy to be used in this trial is non-myeloablative, but where there is concern about a patient’s bone marrow reserves, for example due to multiple previous lines of myelosuppressive chemotherapy a backup stem cell harvest should also be obtained.
13. Female patients of child-bearing potential must have a negative serum or urine pregnancy test prior treatment and agree to use appropriate medically approved contraceptive precautions for four weeks prior to entering the trial, during the trial, and for six months afterwards.
14. Male patients must agree to use barrier method contraception during the treatment and for six months afterwards.
15. Full written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 28; UK Sample Size: 10

Participant exclusion criteria

1. Those receiving radiotherapy, biological therapy, endocrine therapy, immunotherapy, systemic steroids, or chemotherapy during the previous four weeks (six weeks for nitrosoureas and MitomycinC)
prior to treatment or during the course of the treatment.
2. All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade 1 toxicities, which an investigator considers should not exclude the patient.
3. Participation in any other clinical trial within the previous 30 days or during the course of this treatment.
4. Previous allogeneic transplant.
5. Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or Class III or IV AHA criteria for heart disease
6. Patients who are high medical risks because of nonmalignant
systemic disease, including those with, uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which in the lead clinicians opinion would not make the patient a good candidate for adoptive T-cell therapy
7. Concurrent systemic infections (CTCAE Grade 3 or more) within the 28 days prior to treatment.
8. Prior history of malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma
of the cervix uteri and basal or squamous cell carcinoma of the skin.
9. Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
10. History of systemic autoimmune disease which could be lifethreatening if reactivation occurred (for example hypothyroidism would be permissible, prior rheumatoid arthritis or SLE would not).
11. Evidence of CNS involvement.
12. Patients who are likely to require systemic steroids or other immunosuppressive therapy.
13. Pregnant and lactating women.
14. Radiotherapy to >25% skeleton.

Recruitment start date

01/10/2014

Recruitment end date

01/05/2018

Locations

Countries of recruitment

France, Italy, Netherlands, Sweden, United Kingdom

Trial participating centre

Christie Hospital NHS Foundation Trust
Manchester
M20 4BX
United Kingdom

Sponsor information

Organisation

Christie Hospital NHS Foundation Trust (UK)

Sponsor details

550 Wilmslow Road
Manchester
M20 4BX
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.christie.nhs.uk/

Funders

Funder type

Government

Funder name

Seventh Framework Programme

Alternative name(s)

EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes