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

ISRCTN ISRCTN83343031
DOI https://doi.org/10.1186/ISRCTN83343031
Protocol serial number 14133
Sponsor Christie Hospital NHS Foundation Trust (UK)
Funder Seventh Framework Programme
Submission date
10/09/2013
Registration date
10/09/2013
Last edited
05/03/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-t-cell-therapy-for-cancer-of-the-oesophagus-or-stomach

Contact information

Mr Ian Emerson
Scientific

Christie Hospital NHS Foundation Trust
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom

Ian.emerson@christie.nhs.uk

Study information

Primary study designInterventional
Study designPhase II open-label non-randomised interventional treatment trial
Secondary study designNon randomised study
Scientific titleA Phase II Trial to Assess the Activity of NY-ES-O1 Targeted T Cells in Advanced Oesophagogastric Cancer
Study acronymATTACK-OG
Study objectivesThis 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(s)13/SS/0041
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Oesophagus, Stomach
InterventionInterluekin 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 typeBiological/Vaccine
PhasePhase II
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)

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

Key secondary outcome measure(s)

Not provided at time of registration

Completion date01/05/2018

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration28
Key inclusion criteriaPrescreening:
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
Key exclusion criteria1. 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.
Date of first enrolment01/10/2014
Date of final enrolment01/05/2018

Locations

Countries of recruitment

  • United Kingdom
  • England
  • France
  • Italy
  • Netherlands
  • Sweden

Study participating centre

Christie Hospital NHS Foundation Trust
Manchester
M20 4BX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No

Editorial Notes

05/03/2019: Internal review.

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