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

Phase 2

Completed

• Conditions: Cancer; Topic: National Cancer Research Network; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Oesophagus, Stomach; Malignant neoplasm of oesophagus

• Registration Number: ISRCTN83343031
• Lead Sponsor: Christie Hospital NHS Foundation Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-09-10
• Study Completion: 2018-05-01
• Last Update Posted: 25 March 2019

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 28

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

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
ot provided at time of registration