Advanced Gastric/Oesophageal Adenocarcinoma
Conditions
Interventions
Product Name: Ticilimumab
Product Code: CP-675, 206
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ticilimumab (fully human IgG2 monoclonal antibody)
CAS Number: 745013-59-6
Current
Sponsors
Christie Hospital NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for the study, patients must satisfy all of the following criteria: 1. Histologically confirmed gastric or oesophageal adenocarcinoma that is locally advanced or metastatic. 2. Prior treatment with appropriate chemotherapy. 3. Patients with persistent or progressive disease post chemotherapy or patients who could not tolerate previous treatment due to unacceptable toxicity. 4. A minimum of one measurable lesion on CT scan according to RECIST. See Appendix 2 for details. 5. ECOG performance status (PS) 0 or 1. 6. Life expectancy > 3 months. 7. Age = 18 years. 8. Female patients must be surgically sterile or be postmenopausal for at least two years, or must agree to use effective contraception during the period of treatment and 6 months after. Women of child bearing potential must have a negative pregnancy test prior to entry and within 72 hours prior to receiving each cycle of ticilimumab. 9. Adequate bone marrow, hepatic and renal function determined within 14 days prior to enrollment, defined as: • Absolute neutrophil count = 1.5 x 109 cells/L • Platelets = 100 x 109 cells/L • Haemoglobin = 9.0g/dL • Aspartate and Alanine aminotransferases (AST, ALT) = 2.5 x ULN 5 x ULN if documented liver metastases are present) • Total bilirubin = 2 x ULN (except for patients with documented Gilbert’s syndrome) • Serum creatinine =170µmol/L 10. Patients must have recovered from all prior treatment-related toxicities, to baseline status, or to NCI CTCAE v3 Grade 0 or 1, except for toxicities not considered a safety risk such as alopecia or residual peripheral neuropathy resulting from prior systemic therapy. Post-surgical pain shall not be considered a basis for exclusion. 11. Must be willing and able to provide written informed consent. 12. Must be willing and able to comply with Study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Received treatment for cancer within 4 weeks prior to enrollment (dosing), 12 weeks for immunotherapy. 2. Received any prior anti-CTLA4-inhibiting agent. 3. History of, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg Addison’s disease, multiple sclerosis, Graves disease, Hashimoto’s thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders etc.). Vitiligo will not be a basis for exclusion. 4. History of, or clinically apparent hepatitis B or hepatitis C. 5. History of inflammatory bowel disease, celiac disease or other chronic gastrointestinal conditions associated with diarrhoea or bleeding, or current acute colitis of any origin. 6. Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (Note: inhaled or topical steroids in standard doses are allowed). 7. Known brain metastases. 8. Prior or concurrent malignancy within the last 5 years other than basal cell carcinoma or in situ carcinoma of the uterine cervix. 9. Evidence of uncontrolled cardiac or respiratory disease or other serious medical or psychiatric disorders that would be a contra-indication to study procedures. 10. Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the study. 11. Pregnancy or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the antitumour-efficacy, as determined by objective response rate, of intravenous ticilimumab administered at a dose of 15mg/kg every 90 days to patients with advanced or metastatic gastric or oesophageal adenocarcinoma;Secondary Objective: Clinical • To assess additional evidence of anti-tumour activity as measured by best on-study response rate, durable response rate, duration of response, progression-free survival and overall survival (see section 14.5 for definitions) • To characterize the safety profile and tolerability of ticilimumab in this setting Laboratory • To assess IL2 release in response to SEA • To assess the changes in lymphocyte immunophenotype following ticilimumab • To evaluate immune responses to 5T4 tumour associated antigen following ticilimumab;Primary end point(s): Best Overall Response (BR) based on Response Evaluation Criteria in Solid Tumours (RECIST)1 and defined as the proportion of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of evaluable patients. | — |
Countries
United Kingdom
Outcome results
None listed