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 : Unknown
Verified August 2016 by Royal Marsden NHS Foundation Trust.
Recruitment status was: Recruiting
First Posted : August 31, 2016
Last Update Posted : August 31, 2016
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Proof-of-concept Study of Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma|
|Study Start Date :||July 2016|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||July 2019|
ibrutinib delivered orally at a dose of 560mg once daily continuously on a 4 weekly cycle until disease progression or unacceptable toxicity occurs.
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.
- 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).
- 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.
- 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.
- 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.
- 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)
- 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.
- 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.
- 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
- 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
- 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
- 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
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
|Contact: Ye mong To||0208 661 firstname.lastname@example.org|
|Contact: Michael Davidson||020 8642 6011 ext email@example.com|
|The Royal Marsden NHS Trust||Recruiting|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Contact: Ye mong To 0208 661 3807 firstname.lastname@example.org|
|Contact: Michael Davidson 020 8642 6011 ext 4374|
|Principal Investigator: Ian Chau|
|Sub-Investigator: Michael Davidson|
|Sub-Investigator: Irene Chong|
|Study Chair:||Ian Chau||Royal Marsden NHS Foundation Trust|