Her2 or cMYC positive advanced oesophagogastric carcinomas
Conditions
Interventions
Trade Name: Ibrutinib
Product Name: Ibrutinib
Product Code: JNJ-54179060
Pharmaceutical Form: Capsule
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Current Sponsor code: JNJ-54179060
Other d
Sponsors
The Royal Marsden NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research objective is to ascertain whether ibrutinib shows anti-cancer activity in oesophagogastric cancers showing amplifications of either the cMYC gene, the HER2 gene, or co-amplification of both.;Primary end point(s): The primary outcome measure is best overall response rate defined as confirmed by CR and PR (assessed according to RECIST 1.1) and will be presented as a proportion with a 95% confidence interval.;Secondary Objective: The secondary research objectives are to assess the safety and tolerability of ibrutinib in patients with oesophagogastric cancers and to correlate the anti-cancer activity of ibrutinib with changes seen on PET-CT scanning. Further exploratory objectives of ths study include: -correlating the anti-cancer effect of ibrutinib with changes in DNA and circulating tumour cells in the blood and in the cancer itself through the use additional optional biopsies -correlating the anti-cancer effect of ibrutinib with changes in the HER2 and cMYC genes as well as other proteins that they have an effect on -preparing tissue arrays to develop molecular signatures of response and resistance to ibrutinib treatment -collecting and storing plasma, serum and archival and serial tumour biopsies for potential future exploratory research into factors that may influence development and progression of cancer and/or response to ibrutinib | — |
Countries
United Kingdom
Contacts
Public ContactMs Ye mong To
The Royal Marsden NHS Foundation Trust
Outcome results
None listed