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Trial record 11 of 318 for:    ibrutinib

Proof-of-concept Study of Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma (iMYC)

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ClinicalTrials.gov Identifier: NCT02884453
Recruitment Status : Recruiting
First Posted : August 31, 2016
Last Update Posted : September 18, 2019
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Brief Summary:

Some cancers of the oesophagus and stomach express excessive copies of either the cMYC (Myelocytomatosis oncogene) gene, the HER2 (Human epidermal growth factor receptor 2) gene or both. These genes may potentially contribute to the growth and spread of cancer.Ibrutinib is a drug that is already used in the treatment of certain cancers of the immune system.

There is preclinical evidence that it shows activity against gastric and stomach cancer cells over-expressing cMYC and HER2 genes.

The iMYC study will assess the activity of ibrutinib in cancers of the oesophagus and stomach which over-express these genes and which have previously been treated with standard chemotherapies.

Any anti-cancer activity seen will be measured and correlated with metabolic changes on FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) - PET (positron emission tomography) scan, changes in DNA and circulating tumour cells in the blood, and molecular changes in the cancer itself through the use of optional repeat tumour biopsies. If an effect is seen it could provide justification for further research in this group of patients.

Patients will be eligible if they have advanced cancer of the oesophagus or stomach and have been treated with at least one line of prior therapy. The study will be conducted at the Royal Marsden Hospital at its Sutton and Chelsea sites.

It will involve an initial group of up to 17 patients. Screening, recruitment and follow up will last for 3 years in total.

Patients wishing to take part must consent to having their cancer biopsied to test for cMYC and HER2 amplification, as well as a number of imaging and blood tests. There are optional further tumour biopsies whilst on study.

Patients will be treated with ibrutinib until progression of their disease or unacceptable toxicity.


Condition or disease Intervention/treatment Phase
Gastrooesophageal Cancer Drug: ibrutinib Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Proof-of-concept Study of Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma
Actual Study Start Date : July 19, 2016
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: ibrutinib
ibrutinib delivered orally at a dose of 560mg once daily continuously on a 4 weekly cycle until disease progression or unacceptable toxicity occurs.
Drug: ibrutinib
Ibrutinib (PCI-32765) is a first-in-class, potent, orally-administered, covalently-binding small molecule inhibitor of Bruton's tyrosine kinase (BTK) currently under development for the treatment of B-cell malignancies. Ibrutinib is being co-developed by Janssen Research & Development, LLC and Pharmacyclics Inc.
Other Names:
  • JNJ-54179060
  • IMBRUVICA
  • PCI-32765




Primary Outcome Measures :
  1. Objective response rate in patients with c-MYC and HER2 amplified advanced pre-treated oesophagogastric carcinomas treated with ibrutinib [ Time Frame: 3 years ]
    Primary end point of objective overall radiological response rate, defined as confirmed complete response and partial response on CT or MRI imaging (assessed according to RECIST 1.1).


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 3 years ]
    Defined as time from start of study treatment to disease progression or death from any cause. Will be analysed using the Kaplan-Meier method and the results presented as median survival with 95% confidence intervals.

  2. Overall survival [ Time Frame: 3 years ]
    defined as time from start of study treatment to death of any cause. Will be analysed using the Kaplan-Meier method and the results presented as median survival with 95% confidence intervals.

  3. Disease control rate at 8 weeks [ Time Frame: 8 weeks ]
    Proportion of patients with disease control (defined as complete response, partial response or stable disease by RECIST 1.1 on CT or MRI imaging) at 8 weeks.

  4. Safety and tolerability of ibrutinib treatment in advanced oesophagogastric cancer [ Time Frame: 3 years ]
    Assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis), vital signs & number of participants with adverse events (as assessed by CTCAE version 4)

  5. Patient reported outcome- health related quality of life (HRQoL) as assessed by EORTC Quality of Life questionnaire QLQ-C30 [ Time Frame: 3 years ]
    Quality of life subscale scores and change in subscale scores from baseline will be summarised separately by descriptive statistics (mean, median, standard deviation (SD), minimum, maximum) and presented graphically.

  6. Patient reported outcome- health related quality of life (HRQoL) as assessed by EORTC Quality of Life questionnaire STO22 [ Time Frame: 3 years ]
    Quality of life subscale scores and change in subscale scores from baseline will be summarised separately by descriptive statistics (mean, median, standard deviation (SD), minimum, maximum) and presented graphically.

  7. Correlate metabolic changes on FDG-PET scan with changes in gene expression, circulating tumour cells and CT response [ Time Frame: 3 years ]
    FDG-PET scan at baseline and day 14 will be correlated with changes seen in gene expression, circulating tumour cells and clinical response


Other Outcome Measures:
  1. Pharmacokinetics of ibrutinib in advanced oesophagogastric cancer patients: Minimum Concentration (Cmin) of ibrutinib [ Time Frame: 3 years ]
    Blood tests cycle 1 day 8 and cycle 1 day 14

  2. Investigate dynamic changes in c-MYC copy number in circulating tumour DNA [ Time Frame: 3 years ]
    Blood tests at pre screening, screening, cycle 1 day 14 and every 8 weeks whilst on treatment. Mandatory biopsy at screening, optional biopsies at day 14, disease response and progression

  3. Correlate c-MYC amplification ratio in tumour tissue with c-MYC copy number variation in serum [ Time Frame: 3 years ]
    Blood tests at pre screening, screening, cycle 1 day 14 and every 8 weeks whilst on treatment.Mandatory biopsy at screening, optional biopsies at day 14, disease response and progression



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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 abnormalities 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02884453


Contacts
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Contact: Annette Bryant 0208 642 6011 ext 4449 annette.bryant@rmh.nhs.uk
Contact: Michael Davidson 020 8642 6011 ext 4374 michael.davidson@rmh.nhs.uk

Locations
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United Kingdom
The Royal Marsden NHS Trust Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Ye mong To    0208 661 3807    yemong.to@rmh.nhs.uk   
Contact: Michael Davidson    020 8642 6011 ext 4374      
Principal Investigator: Ian Chau         
Sub-Investigator: Michael Davidson         
Sub-Investigator: Irene Chong         
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Janssen, LP
Investigators
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Study Chair: Ian Chau Royal Marsden NHS Foundation Trust

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02884453     History of Changes
Other Study ID Numbers: 4449
First Posted: August 31, 2016    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Royal Marsden NHS Foundation Trust:
gastrooesophageal carcinoma
Additional relevant MeSH terms:
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Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms