FEASIBILITY of IBIS 3. An International Breast Intervention Study investiga... | Recruiting
FEASIBILITY of IBIS 3. An Internati... | Recruiting
FEASIBILITY of IBIS 3. An International Breast Intervention Study investigating prevention of late recurrence in ER+ breast cancer survivors following 5 years of adjuvant treatment
IBIS 3 (Feasibility)

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Medical Conditions
  • Hormone receptor positive breast cancer recurrence
Primary Contact Details
Miss Jill Knox
+44 (0)20 7882 3510
See all trial contact details
Recruitment Status
Recruiting
Trial source and source ID number
ISRCTN93764730
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-extended-treatment-following-5-years-hormone-therapy-breast-cancer-ibis-3-feasibility
Research Details
  • IBIS 3 is designed to continue the work of IBIS-I and IBIS-II in determining whether a chemo-preventive strategy towards breast cancer is effective. Late recurrence of oestrogen receptor positive (ER+) breast cancer is a well-known problem, with high recurrence rates being seen for at least 20 years after diagnosis. In fact, over half of all recurrences in ER+ breast cancer occur more than 5 years after the primary tumour diagnosis. These include true recurrences and new primary tumours. Although reduced from about 2.5%/year with tamoxifen to 2%/year with 5 years of an aromatase inhibitor in the ATAC trial, the 10 year recurrence rate does not fall below 2%/year (Cuzick et al, 2010). The ATAC trial indicates that ER, PgR and HER2 do not provide substantial prognostic information in the post 5-year treatment period. It shows that Ki-67 has a minimal effect whereas baseline nodal status and tumour size (≥ 2cm) continue to have prognostic value (Sestak et al, 2013).

    Late re-treatment of breast cancer is an important approach for dealing with the problem of late recurrence. Diminished endocrine control is well documented and other new or synergistic approaches are likely to be more effective. This approach will also inform on the preventive action of these agents both alone and in combination not only on elimination of metastases but also on new primary tumours. Because a substantial number of late recurrences are in fact new tumours, this approach will also inform on the preventive action of these agents both alone and in combination.

    The main IBIS 3 trial will directly address the issue of late recurrence in breast cancer survivors. The main goal will be to reduce late recurrence with the combination of three different drug therapies. Specifically, it will evaluate the impact of metformin and/or an aromatase inhibitor (anastrozole or letrozole or exemestane) and/or zoledronic acid in a 2x2x2 factorial trial. Of particular interest will be any positive detection of any synergism between these agents.

    The main trial will explore mechanisms of drug action and identify which patients are at greatest risk of late recurrence, including both local, regional and distant metastases of the primary tumour as well as new tumours (mostly contralateral), using a range of tests which may include circulating tumour DNA, IHC4, PAM50, and tumour methylation profiles.

    This feasibility study will look at the viability of recruiting to the main trial; assess recruitment rates, inform on number of sites required for the main trial, treatment adherence and the use of recruiting through GP surgeries local to sites via the PCRN/LCRN. The study will also determine the feasibility of the use of email for data collection of PROs from patients and assess the acceptability of investigations, such as providing blood samples and questionnaires required for the main trial.

    The decision rule for moving to the main trial will be recruitment of at least 80 patients within a year and that at least 20% of eligible patients approached agree to join the trial.
Phase
Phase III
Study Design
Interventional multi-centre CTIMP RCT 2x2x2 factorial design
Study Type
Interventional
Intervention

Metformin and zoledronic acid will be evaluated when combined with an aromatase inhibitor (anastrozole, letrozole or examestane) in a 2x2x2 factorial design.

Intervention Type
Drug
Primary Outcome Measures
    Primary objective is to determine acceptability and feasibility of recruitment, recruitment rate and number of sites required for main trial.
    Primary endpoint is the recruitment of 100 patients within 12 months. Assessment method is recruitment numbers via randomisation figures and screening logs.
Secondary Outcome Measures
    Secondary objectives are:
    1. To determine reasons for non-participation/drop-outs and address these for main trial (endpoint: recruitment and follow-up of 100 patients; assessment method: analysis of screening logs to understand reasons for non-participation)
    2. To evaluate treatment adherence and reasons for stopping (endpoint: 6 monthly follow-up; assessment method: data collected on CRFs, PROs [FACT-ES, EQ5DL], Kaplan Meier curves)
    3. To determine reasons for non-adherence and address for main trial (endpoint: 6 monthly follow-up; assessment method: data collected on CRFs, PROs [FACT-ES, EQ5DL])
    4. To assess the use of referral through GP surgeries as PICs local to sites via the PCRN/LCRN (endpoint: the recruitment of 100 patients; assessment method: recruitment method captured by CRF and assessment of referral letters)
    5. To investigate feasibility of the use of email for data collection of PROs from patients (enpoint: at baseline + asked again at 12 and 24 months to see if email use increases with time; assessment method: comparison of numbers of patients providing data by email or by post and quality and completeness of that data)
    6. To assess acceptability of investigations for main trial (endpoint: at 12 months and ongoing until trial ends; assessment method: number of patients providing blood samples [data on CRF], PRO data [FACT-ES, EQ5DL])
Publication(s)
Sorry, this information is not available
Result Reports
Sorry, this information is not available
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
Female
Age Range
Adult
Who Can Participate
Patient
Number of Participants
300
Participant Inclusion Criteria
    Current inclusion criteria as of 30/03/2017:
    1. Informed Consent
    2. ≤ 75 years
    3. Post-menopausal women confirmed by previous AI use only
    4. Previous ER+ breast cancer treated by endocrine therapy. ER+ is equivalent to an Allred/Quick score of 3 or above. Additional treatment with trastuzumab (if Her2+) and chemotherapy are allowed.
    5. Surgery for breast cancer plus 5 years adjuvant endocrine therapy (at least 4 years with AI completed within the last 6 years; therefore 5-11 years from diagnosis)
    6. Breast cancer must have been node positive AND/OR ≥2cm in size (measurement based on invasive tumour)
    7. A bilateral mammogram (unless unilateral mastectomy in which case unilateral mammogram) must have been taken within the last year and not show any evidence of breast cancer. Women who have had a bilateral mastectomy, where contralateral mastectomy was either prophylactic or was performed to treat breast cancers diagnosed at the same time, are eligible and a mammogram is not required in this case.
    8. A baseline bone mineral density (BMD) scan within the last year; DXA must include hip (femoral neck or proximal femur) AND lumbar spine and can include forearm.
    9. Low BMD (where T-score is -4.0 ≤T≤ -2.0) women are eligible for metformin and aromatase inhibitor treatments. This must be managed in accordance with local clinical procedures for treatment of osteoporosis i.e., take bisphosphonate treatment and have regular DXA scans

    Previous inclusion criteria:
    1. Informed consent
    2. ≤ 75 years old
    3. Post-menopausal women (defined as at least 12 months since last period)
    4. Previous ER+ (or PR+) breast cancer treated by endocrine therapy. ER+ is equivalent to an Allred/Quick score of 3 or above. Additional trastuzumab (if Her2+) and chemotherapy are allowed.
    5. Surgery for breast cancer plus 4-6 years adjuvant endocrine therapy (at least 4 years with AI completed within the last 3 years; therefore maximum of 9 years from diagnosis)
    6. Breast cancer must have been node positive (macrometastases) AND/OR ≥2cm
    7. A bilateral mammogram (unless unilateral mastectomy in which case unilateral mammogram) must have been taken within the last year and not show any evidence of breast cancer. Women who have had a bilateral mastectomy are eligible and a mammogram is not required in this case.
    8. A baseline bone mineral density scan within the last year; DXA must include hip (femoral neck or proximal femur) AND lumbar spine and can include forearm.
    9. Low BMD (where T-score is -4.0 ≤T≤ -2.0) and no more than one known low trauma vertebral fracture AND/OR high FRAX score (http://www.shef.ac.uk/FRAX/tool.aspx) are eligible for metformin and aromatase inhibitor treatments. This must be managed in accordance with local clinical procedures for treatment of osteoporosis i.e., take bisphosphonate treatment and have regular DXA scans.
Participant Exclusion Criteria
    Current exclusion criteria as of 30/03/2017:
    1. Any recurrence or clinical suspicion of active breast cancer (including DCIS)
    2. Any other previous cancer (apart from original breast cancer) (except non-melanoma skin cancer or in situ cancer of the cervix).
    3. Current (or intended) use of oestrogen-based hormone replacement therapy (HRT)
    4. Type I diabetes
    5. Type II diabetes AND osteoporosis
    6. T-scores of less than minus four, or two or more known low trauma vertebral fractures
    7. Abnormal renal function as classified as eGFR < 45mls/min. – If possible the CKD-EP1 equation should be used to calculate eGFR but the Cockroft-Gault formula is acceptable. See Appendix 3 for formulae and dose reduction schedule.
    8. Any severe concomitant disease, e.g congestive cardiac failure, that would, at the discretion of the investigator, put patient at unusual risk or confounds the results of the study. Reference should be made to the appropriate Summary of Product Characteristics (SmPC) of each study drug
    9. Current continual treatment with glucocorticoids for 4 weeks or more
    10. Any medical condition that would significantly interfere with the ability to accept the study drugs.
    11. Psychologically and physically unsuitable for two years of drug therapy.
    12. Treatment with an unlicensed or experimental drug during 30 days before randomisation.

    Excluded from metformin randomisation only
    13. Type II diabetics (or those with baseline fasting glucose > 7.0 mmol/L) but must be on antidiabetic medication
    14. Known hypersensitivity or intolerance to metformin
    15. Currently taking meglitinides, sulfonylureas, thiazolidinediones (glitazones) or insulin
    16. History of acidosis of any type
    17. Habitual intake of 3 or more units of alcohol per day

    Excluded from zoledronic randomisation only
    18. Low BMD (where T-score is -4.0 ≤T≤ -2.0). This must be managed in accordance with local clinical procedures for treatment of osteoporosis i.e., take bisphosphonate treatment and have regular DXA scans. See Appendix 4 for definitions.

    Excluded from AI randomisation only
    19. Currently being treated by extended AI
    20. Current use (or intention to use) raloxifene, tamoxifen or any other SERM

    Previous exclusion criteria:
    1. Any recurrence or clinical suspicion of active breast cancer (including DCIS)
    2. Any other previous cancer (apart from original breast cancer) in the past 5 years (except non-melanoma skin cancer or in situ cancer of the cervix)
    3. Current treatment (or intended use) of oestrogen-based hormone replacement therapy (HRT)
    4. Type I diabetes
    5. Diabetes (Types I and II) AND osteoporosis
    6. T-scores of less than minus four, or two or more known low trauma vertebral fractures
    7. Abnormal renal function as classified as eGFR < 40ml/min. If possible the CKD-EP1 equation should be used to calculate eGFR but the Cockroft-Gault formula is acceptable
    8. Any severe concomitant disease, e.g. congestive cardiac failure, that would, at the discretion of the investigator, put patient at unusual risk or confounds the results of the study. Reference should be made to the appropriate Summary of Product Characteristics (SmPC) of each study drug
    9. Current continual treatment with glucocorticoids for 4 weeks or more
    10. Any medical condition that would significantly interfere with the ability to accept the study drugs
    11. Psychologically and physically unsuitable for two years of drug therapy
    12. Treatment with an unlicensed or experimental drug during 30 days before randomisation

    Excluded from metformin randomisation only:
    1. Type II diabetics (or those with baseline fasting glucose > 7.0 mmol/L) but must be on antidiabetic medication
    2. Known hypersensitivity or intolerance to metformin
    3. Currently taking meglitinides, sulfonylureas, thiazolidinediones (glitazones) or insulin
    4. History of acidosis of any type
    5. Habitual intake of three or more units of alcohol per day

    Excluded from zoledronic randomisation only:
    1. Low BMD (where T-score is -4.0 ≤T≤ -2.0) and no more than one known low trauma vertebral fracture AND/OR high FRAX score (http://www.shef.ac.uk/FRAX/tool.aspx)

    Excluded from AI randomisation only:
    1. Currently being treated by extended AI
    2. Current use (or intention to use) raloxifene, tamoxifen or any other SERM
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
North Shields
NE29 8NH
Manchester
M20 4BX
Edinburgh Cancer Centre at Western General Hospital
Edinburgh
Scotland
EH4 2XU
London
EC1A 7BE
Rheumatology Department, Poole Hospital NHS Trust
Poole
BH15 2JB
Kennedy Institute Clinical Trials Unit, 4Wl, Charing Cross Hospital
London
W6 8RF
Dundee
DD1 9SY
Doncaster
DN2 5LT
Cardiff
CF14 4XW
Pinderfields General Hospital
Wakefield
Scotland
WF1 4DG
Sheffield
S10 2SJ
Macclesfield District General Hospital
Macclesfield
SK10 3BL
Borders General Hospital
Melrose
TD6 9BS
Trial Contact(s)
Primary Trial Contact
Miss Jill Knox
+44 (0)20 7882 3510
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
FEASIBILITY of IBIS 3. An International Breast Intervention Study investigating prevention of late recurrence in ER+ breast cancer survivors following 5 years of adjuvant treatment
EudraCT Number
2014-004430-26
Funder(s)
  • Cancer Research UK
  • Australia and New Zealand Breast Cancer Trials Group (ANZBCTG)
Other Study ID Numbers
N/A
Sponsor(s)
Queen Mary University of London
Key Dates

Recruitment Start Date

26 Sep 2016

Recruitment End Date

25 Sep 2018

Trial Start Date

01 Jan 2014

Trial End Date

31 Dec 2018

Date added to source

11 Dec 2014

Date updated in source

31 Mar 2017