metastatic or locally advanced colorectal cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: AZD8931 film-coated tablet 20 mg
Product Code: AZD8931
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AZD8931 Difumarate (INN: sapitinib)
CAS Number: 1196531-39-1
Current
L001739996-008U, AZ13737568 hemihydrate
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 25-100
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female patients at least 18 years old at registration 2.FFPE tumour block taken prior to the commencement of standard first-line treatment and available for biomarker analysis 3.Histologically confirmed adenocarcinoma of the small bowel or colon or rectum 4.Inoperable metastatic or locoregional disease (synchronous or metachronous) 5.WHO performance status 0, 1 or 2 (see Appendix III) 6.Disease which could be RECIST reported v1.1 classification as unidimensionally measurable disease (see Appendix IV) from the CT scan taken following inclusion criteria 7. 7.Have had an electronically accessible CT scan performed. This scan should ideally be performed just before but no more than six weeks prior to commencement of standard first-line treatment. Unavoidable delays of a few days for scheduling reasons may be approvable, but sites must contact the MRC CTU prior to registering the patient. CT scans performed a few days after the start date of standard first-line treatment may also be approvable, but only due to uncontrollable circumstances and only after discussion with the MRC CTU team and prior to registering the patient. 8.Women of child bearing potential must be willing to use adequate contraceptive measures (see Appendix V for contraindications of oral contraceptives) from registration into FOCUS4 to 7 weeks after ending first-line treatment and during, and 6 weeks after any subsequent randomised treatment in one of the FOCUS4 comparisons, should not be breastfeeding and must have a negative pregnancy test at any point prior to registration. Women of non-child bearing potential should fulfil one of the following criteria at screening: Post menopausal as defined by: Aged =50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments Aged <50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and with luteinising hormone and follicular stimulating hormone levels in the post-menopausal range Documentation of irreversible surgical sterilisation by hysterectomy, and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal ligation 9.Male patients with partners of child bearing potential should be willing to abstain or use barrier contraception (i.e., condoms) for the duration of standard first-line treatment following registration and for 3 months after stopping any treatment administered as part of FOCUS4 (standard first line treatment, or subsequent randomised treatment). Male patients wishing to father children whilst taking standard first-line treatment and 3 months after stopping standard first-line treatment should be counselled on freezing sperm samples before starting standard first-line treatment. 10.Consent for screening of an archival FFPE tumour block for biomarker analysis 11.Patients who have already commenced on standard first-line treatment must be registered for the trial during the first 12 weeks of first-line treatment (this allows approximately 6 weeks for return of their biomarker results prior to the end of first-line treatment) 12.Patients should have sufficient capacity for informed consent assessed at the treating physicians discretion 13.Patient has provided signed informed consent For inclusion criteria for randomisation into FOCUS4-C, please refer to section 3.3.1 of the FOCUS4-C protocol v6.0 dated 17.09.2019. For inclusion criteria for randomisation into FOCUS4-N, pleas
Exclusion criteria
Exclusion criteria: 1.Any previous systemic palliative chemotherapy for established advanced or metastatic disease except single agent capecitabine as a radiosentiser in a setting with potential curative intent such as leading to possible resection. 2.Adjuvant chemotherapy given in the 6 months prior to commencing standard first-line treatment 3.Patients with brain metastases 4.Pregnant and lactating women 5.Patients with known HIV, hepatitis B or hepatitis C infection For exclusion criteria for randomisation into FOCUS4-C, please refer to section 3.3.2 of the FOCUS4-C protocol v6.0 dated 17.09.2019. For exclusion criteria for randomisation into FOCUS4-N, please refer to section 3.3.2 of the FOCUS4-N protocol v5.0 dated 11.09.2019.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are: 1) For patients with the same tumour type (characterised by the results of the molecular tests), do the proposed new agents significantly increase the length of time for a patient to die, or for their tumour to increase in size by at least 20% when compared to patients having a treatment break after their first-line chemotherapy, in the time period after standard first-line? 2) Do the patients who have a particular genetic mutation identified by the molecular tests respond better to a proposed new agent than the patients who do not have that particular mutation? ;Secondary Objective: Secondary research questions are: 1) Do the patients taking the proposed new agents experience an unacceptably higher level of toxicity symptoms and side-effects compared to the patients in the no treatment comparison group? 2) Are there any differences in safety outcomes (eg. occurence of heart or kidney disease) between the patients taking the proposed new agents and those in the no treatment comparison group? 3) Does quality of life (measured by the EuroQol 5D questionnaire) differ between the patients taking the proposed new agents and those in the no treatment comparison group? This is currently only applicable to patients in FOCUS4-N.;Primary end point(s): There are no primary outcome measures for the registration period as no interventions are being compared during this period. The primary outcome measure for the subsequent FOCUS4 comparisons that commence at the end of the registration period will be Progression-Free Survival (PFS) defined as progression of disease according to RECIST v1.1 criteria or death from any cause. Analysis will be timed from randomisation with the baseline CT scan performed within 4 weeks prior to randomisation. For trials that complete Stage III, at this point, a decision will be made on whether to revise power calculations to include Overall Survival (OS) as an additional primary outcome measure. ;T | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes will include evaluation of disease control, safety and toxicity starting from time of randomisation. In some instances measurement of quality of life using the EuroQol 5D questionnaire may be used for trials that proceed beyond Stage II.;Timepoint(s) of evaluation of this end point: Analysis of the secondary endpoints is likely to coincide with the analyses for the primary outcomes but this will be at the discretion of the IDMC. | — |
Countries
United Kingdom
Contacts
Public ContactMarta Campos
University College London
Outcome results
None listed