The iMYC study to assess the effectiveness and safety of ibrutinib in patients with advanced oesophagogastric cancer with c-MYC and HER2 gene amplificatio

Phase 1

Conditions: Her2 or cMYC positive advanced oesophagogastric carcinomas
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-005525-39-GB

Lead Sponsor: The Royal Marsden NHS Foundation Trust

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

-Provision of signed and dated, written informed consent prior to any study specific procedures.
-Female or male aged 18 years or older.
-Histologically proven metastatic or locally advanced inoperable squamous or adeno carcinoma of the oesophagus, stomach or oesophago-gastric junction.
-Documented progression after at least 1 prior line of chemotherapy for advanced disease. For HER2 positive tumours documented progression after at least 1 line of chemotherapy with or without HER2 directed therapy.
-c-MYC or HER2 gene amplification as defined in trial protocol
-Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study. If female patients are taking hormonal contraceptives to prevent pregnancy then this should be combined with a barrier method of contraception. Men must agree to not donate sperm during and after the study. For both males and females restrictions apply for 3 month after the last dose of study drug. See protocol for highly effective methods of birth control.
-Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [b-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study.
-Mandatory provision of archival or fresh tumour biopsy for confirmation of c-MYC or HER2 gene amplification.
-World Health Organisation (ECOG) performance status 0-2, minimum life expectancy of 12 weeks from proposed first dose date, no deterioration within 2 weeks of screening and first dose.
-Adequate organ and haematological function as evidenced by the following laboratory values within 14 days before enrolment:

absolute neutrophil count (ANC) =1,500/mm3µL
platelets =100,000/mm3µL (independent of transfusion support)
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 x upper limit of normal (ULN)
total bilirubin =1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
serum creatinine =2 x ULN or estimated creatinine clearance (CCr) =30 mL/min/1.73m2

-At least one measurable target lesion, as per RECIST criteria 1.1

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion Criteria

-Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
-Concurrent treatment within 4 weeks of study entry with any other chemotherapy, anticancer immunotherapy or experimental therapy
-No available histology for c-MYC or HER-2 amplification testing
-Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
-Patients with ECG abrnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc)
-Any actively bleeding gastrooesophageal tumour
-History of stroke or intracranial haemorrhage within 6 months prior to enrolment
-Symptomatic brain metastases
-Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
-Ongoing anticoagulation with a vitamin K antagonist
-Requiring use of strong P450 (CYP) 3A4 inhibitors
-Major surgery within 4 weeks of enrolment
-Vaccinated with live, attenuated vaccines within 4 weeks of enrolment
-Any pre-existing medical condition of sufficient severity to prevent full compliance with the study