A Phase II Trial to Assess the Activity of NY-ESO-1 Targeted T Cells in Advanced Oesophagogastric Cancer
- Patients must have histologically confirmed oesophagogastric cancer with confirmed
evidence of metastatic disease and to have failed or refused standard therapies.
- There must be measurable disease
- Patients may have had any previous systemic therapies provided they are otherwise fit
- Age equal to or greater than 18 years
- World Health Organisation (WHO) performance status of 0 or 1
- Patients must be HLA-A2 positive
- Their tumour must stain positive by immunohistochemistry for NY-ESO-1 (either
diagnostic or more recent biopsy is acceptable)
- Life expectancy >3months
- Left ventricular ejection fraction (LVEF) > 50% as measured by ECHO or Multi Gated
Acquisition Scan (MUGA)
- Haematological and biochemical indices:
- Haemoglobin (Hb) ≥ 8.0 g/dL
- Neutrophils ≥ 1.0 x 10*9/L
- Platelets (Plts) ≥ 100 x 10*9/L
- Any of the following abnormal baseline liver function tests:
- serum bilirubin ≤ 20 mmol/l (ULN)
- alanine aminotransferase (ALT) and/or
- aspartate aminotransferase (AST) and/or
- ≤ 3 x ULN unless patient has liver metastases when can be < 5 x ULN.
- Serum creatinine ≤ 0.15 mmol/L or creatinine clearance > 50 ml/min
- These measurements must be performed prior to leukaphereses and again prior to
commencing preconditioning chemotherapy.
- The chemotherapy to be used in this trial is non-myeloablative, but where patients
have had previous high dose chemotherapy, an autologous haemopoietic stem cell backup
harvest, for stem cell rescue, will be obtained prior to commencing therapy in this
trial. Similarly, 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.
- 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.
- Male patients must agree to use barrier method contraception during the treatment and
for six months afterwards.
- Able to provide full written informed consent.
- Those receiving radiotherapy, biological therapy, endocrine therapy, immunotherapy,
systemic steroids, or chemotherapy during the previous four weeks (six weeks for
nitrosoureas and Mitomycin-C) prior to treatment or during the course of the
- 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.
- Participation in any other clinical trial within the previous 30 days or during the
course of this treatment.
- Previous allogeneic transplant.
- Clinically significant cardiac disease.
- Patients who are high medical risks because of non-malignant systemic disease,
including those with active infection, 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.
- Concurrent serious infections within the 28 days prior to treatment
- Current 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.
- Patients known or found to be serologically positive for Hepatitis B, C, HIV or Human
T cell lymphotropic Virus (HTLV).
- History of systemic autoimmune disease which could be life-threatening if
reactivation occurred( for example hypothyroidism would be permissible, prior
rheumatoid arthritis or systemic lupus erythematosus (SLE0 would not).
- Evidence of Centra Nervous System (CNS) involvement.
- Patients who are likely to require systemic steroids or other immunosuppressive
- Pregnant and lactating women.
- Radiotherapy to >25% skeleton.