FOCUS4: Molecular selection of therapy in colorectal cancer | Recruiting
FOCUS4: Molecular selection of ther... | Recruiting
FOCUS4: Molecular selection of therapy in colorectal cancer
FOCUS4

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Medical Conditions
  • Topic: National Cancer Research Network
  • Subtopic: Colorectal Cancer
  • Disease: Colon, Rectum
Primary Contact Details
Recruitment Status
Recruiting
Trial source and source ID number
ISRCTN90061546
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
http://www.cancerresearchuk.org/cancer-help/trials/a-trial-looking-at-different-treatments-for-different-types-of-bowel-cancer-focus4
Research Details
  • FOCUS4 is an umbrella, or platform, for testing novel agents in biomarker-defined subpopulations of first-line advanced disease colorectal cancer patients who are not considered candidates for potentially curative surgery. It is also a trial of a new strategy for testing stratified approaches to therapy in any biologically complex tumour type. See Trial Schema in the Trial Protocol.
    The backbone of the platform is 16 weeks of treatment with any standard first line colorectal cancer treatment, after which, as is frequently standard practice in the UK and Europe, there is a programmed treatment break for responding and stable patients. During that break, either new agent(s) or placebo is administered. The primary outcome measure for assessing the activity of the new treatment is progression free survival in the interval (time to death or progression requiring resumption of chemotherapy).
    At present, four coherent biomarker-stratified groups can be identified and trials will be established in each of these cohorts as follows:
    - BRAF mutant
    - PIK3CA mutation or complete loss of PTEN on IHC
    - KRAS or NRAS mutant
    - All wild type (no mutations of BRAF, PIK3CA, KRAS or NRAS)
    - Unclassified biomarker results
    For each of these subgroups, a relevant novel agent or combination is to be tested in an adaptive double blind randomised trial design with multiple interim analyses for early termination if there is no strong evidence of worthwhile activity (the principles are derived from the Multi-Arm, Multi-Stage (MAMS) design).

    FOCUS4 will open with one molecularly stratified trial (FOCUS4-D) testing AZD8931 (a HER 1,2 3 inhibitor) against placebo in patients stratified into the All wild-type cohort. In addition, a non-stratified trial (FOCUS4-N) will be open for patients whose biomarker results are unclassified or who are unable or unwilling to participate in the molecular trial available to them. The molecularly stratified trials for the BRAF, PIK3CA, KRAS/NRAS mutant cohorts are still in development and will be updated on this site when they open. Target recruitment levels will also be adjusted at that time.
Phase
Not Applicable
Study Design
Randomised; Interventional; Design type: Treatment
Study Type
Interventional
Intervention

AZD8931 (for FOCUS4-D), HER 1,2 3 Inhibitor; Capecitabine (FOCUS4-N), Oral 5FU pro drug
Randomisation is performed using minimisation with a random element. Minimisation factors are based upon known prognostic factors for outcome.

For FOCUS4-D: The trial medication is orally administered twice daily over a continuous 28 day cycle. Patients are followed up every 4 weeks for symptoms and toxicity when they also collect their double-blind placebo controlled prescription from hospital pharmacy. CT scans are performed every 8 weeks to determine progression status of the tumour.

For FOCUS4-N: Capecitabine is an oral administration taken twice daily for 14 days followed by a 7 day break before recommencing the 21 day cycle. All patients from both arms are required to attend an outpatients appointment every 3-4 weeks to assess symptoms and toxicity and for those in the capecitabine arm, they need to collect their next prescription. All patients have a CT scan every 8 weeks to determine progression status of the tumour.

Intervention Type
Drug
Primary Outcome Measures
    Progression Free Survival: determined by multi-stage design of each molecular trial
Secondary Outcome Measures
    Overall Survival: becomes a joint primary outcome if the trial continues to the final stage analysis
Publication(s)
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26350752
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
Both
Age Range
Adult
Who Can Participate
Patient
Number of Participants
Planned Sample Size (based upon FOCUS4-D and FOCUS4-N being open): 384; UK Sample Size: 384; Recruitment will be updated as other trials open
Participant Inclusion Criteria
    Registration Inclusion Criteria (please refer to the protocol for eligibility for randomisation)
    1. Male/female patients at least 18 years old
    2. Formalin fixed paraffin embedded (FFPE) tumour block taken prior to the commencement of standard chemotherapy and available for biomarker analysis
    3. Histologically confirmed adenocarcinoma of the colon/rectum
    4. Inoperable metastatic or locoregional disease (synchronous or metachronous)
    5. WHO performance status 0, 1 or 2
    6. Unidimensionally measurable disease RECIST 1.1 classification
    7. Have had an electronically accessible CT scan performed within 4 weeks prior to start of standard chemotherapy
    8. Platelet count < 400 x 109/L prior to start of standard chemotherapy
    9. For women of childbearing potential, a negative pregnancy test and acceptable contraceptive precautions
    10. Effective contraception for male patients if the risk of conception exists
    11. Consent for screening of an archival FFPE tumour block for biomarker analysis (PIS1 & CF1)
    13. Patients should have sufficient capacity for informed consent and provided signed informed consent
Participant Exclusion Criteria
    Registration Exclusion (please refer to the protocol for eligibility for randomisation)
    1. Previous systemic palliative chemotherapy using a different regimen for established advanced or metastatic disease
    2. Adjuvant chemotherapy given in the last 6 months
    3. Patients with brain metastases
    4. Pregnant and lactating women
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)
Aviation House 125 Kingsway
London
WC2B 6NH
Trial Contact(s)
Primary Trial Contact
Dr Cheryl Pugh
-
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
Molecular selection of therapy in colorectal cancer: a molecularly stratified randomised controlled trial programme
EudraCT Number
2012-005111-12
Funder(s)
  • Cancer Research UK (UK)
  • National Institute for Health Research (NIHR) (UK) - Efficacy and Mechanism Evaluation
  • Grant Codes: 11/100/50
Other Study ID Numbers
14893
Sponsor(s)
The Medical Research Council (MRC) (UK)
Key Dates

Recruitment Start Date

01 Dec 2013

Recruitment End Date

30 Nov 2017

Trial Start Date

01 Dec 2013

Trial End Date

30 Nov 2017

Date added to source

16 Oct 2013

Date updated in source

10 Sep 2015