None listed
Conditions
Interventions
Group 1 Type of group
AZD8931 one Tablet Oral bid + Paclitaxel IV once weekly for 3 weeks followed by a week off (repeated cycles)
Group name:Group 2 Type of group
Paclitaxel IV once weekly for 3 weeks followed by a week off (repeated cycles) + AZD8931 Placebo Oral bid (twice daily)
Sponsors
ASTRAZENECA - PERU,
Eligibility
Sex/Gender
Female
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: • Provision of signed, written informed consent prior to any study specific procedures • Age 18 years and older • Suitable for paclitaxel therapy • Estimated life expectancy of more than 12 weeks • Not previously randomised to treatment in this study • Females must be of non childbearing status defined as one of the following criteria at screening: -negative pregnancy test in women of childbearing potential -women who are permanently or surgically sterilised (hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) -postmenopausal (over 50 years old and amenorrheic for 12 months following cessation of all exogenous hormonal treatments, or over 57 years old) • Females must not be breastfeeding • Female patients of child bearing potential must use an acceptable highly effective method of contraception plus condoms plus spermicide during the study and for 30 days after the last dose of study drug. It is recommended that women should have been stable on their chosen method of contraception for at least 3 months before entering the study. Recommended methods of contraception are listed in Appendix J 9. Patients must not have received an investigational drug within 30 days or 5 half lives, whichever is longer, of the first dose of randomised therapy (AZD8931 or matching placebo) • A haemoglobin =9 g/dL (5.59 mmol/L). [Note: any blood transfusion must be >14 days prior to the determination of a haemoglobin =9 g/dL (5.59 mmol/L)] Phase II only 37. Female patients with histologic or cytologic diagnosis of breast cancer with evidence of locally advanced (not amenable to surgery) or metastatic disease. Lesions should not be amenable to surgery or radiation of curative intent • Patients must not have received previous taxane therapy in an adjuvant or neo-adjuvant setting, within 12 months prior to the start of AZD8931/matching placebo • Patients must not have received taxane therapy for treatment of locally advanced (not amenable to surgery) or metastatic breast cancer • Patients must not have received more than one cytotoxic chemotherapy regimen for the treatment of locally advanced (not amenable to surgery) or metastatic breast cancer. (Previous endocrine therapy for the treatment of the locally advanced, or metastatic breast cancer with endocrine therapy is permitted) • Patients must be deemed ineligible for trastuzumab or lapatinib treatment by local assessment. This should include IHC analysis to determine HER2 status with further testing by FISH/CISH when considered part of local practice. -Tumour tissue sample provision for central analysis is a mandatory part of the screening procedures and must be available. The sample can be taken from archival diagnostic tissue from the original biopsy or a more recent biopsy. Both primary lesion and metastatic sites are acceptable. Notification of patient eligibility will come from the central laboratory informing the site that HER2 expression is within limits for randomisation
Exclusion criteria
Exclusion criteria: • Female patients of child bearing potential must use an acceptable highly effective method of contraception plus condoms plus spermicide during the study and for 30 days after last dose of AZD8931/matching placebo. Recommended methods of contraception are listed in Appendix J • Patients should use sunglasses and sun cream with UVA and UVB protection SPF>30 if exposed to sunlight and avoid use of sun tanning booths during the study and for 3 months after the last dose of IP • Patients who are blood donors should not donate blood during the trial and for 3 months following their last dose of IP • All patients must avoid concomitant use of medications, herbal supplements and/or ingestion of foods that significantly modulate CYP3A4 and/or CYP2D6 activity . Such drugs must have been discontinued for an appropriate period before they enter screening and for a period of 2 weeks after the last dose of AZD8931. Guidance on medications to avoid and on washout periods is given in Appendix D • Refer to the Summary of Product Characteristics (SPC) for restrictions specific to paclitaxel • Male patients (including those that have undergone a successful vasectomy) must use condoms plus spermicide during sexual contact with a female of child-bearing potential who is not using a highly effective method of contraception, for the duration of the study and for 3 months after the last dose of AZD8931 • Male patients will be advised to abstain from sperm donation from first dose until 3 months following receipt of the last dose of AZD8931 • Refrain from driving for 4 hours following ophthalmic examination if pupillary dilatation performed • Patients should refrain from wearing contact lenses from at least 1week prior to starting AZD8931 to 1 week after discontinuation of AZD8931 • Patients who wear contact lenses should discontinue wearing their lenses if they have any mild to moderate eye symptoms (CTCAE grade =2) while receiving treatment with AZD8931/matching placebo until at least one week after symptoms have resolved. If a patient has a recurrence of eye symptoms or experiences any severe (CTCAE grade =3) ocular events they should discontinue wearing their contact lenses until at least one week after treatment with AZD8931/matching placebo is permanently discontinued • Patients should not use any eye drops or ointment for treatment of eye symptoms, unless agreed by a study doctor, at any time during the study until 1 week after AZD8931/matching placebo has been permanently discontinued • Patients should not receive endocrine therapy prior to progression of their disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:DLT is an AE or laboratory abnormality related to AZD8931, starting during the DLT evaluation period and meeting any of the following criteria (further detail in protocol): Symptomatic ocular surface lesion; CTCAE grade 4 haematological AE; CTCAE grade ≥3 of febrile neutropenia / neutropenia / thrombocytopenia / hyperkalaemia / hyperglycaemia / hypotension / urological toxicity / ILD / pneumonitis; QTcF interval > 500 msec, two ECGs ≥ 30 minutes apart; Symptomatic congestive cardiac failure and a drop in LVEF; Decrease in LVEF of ≥20% to below the LLN; CS rash remaining CTCAE grade ≥3 for ≥5 days despite optimal treatment; CTCAE grade ≥3 nausea, vomiting or diarrhoea, despite optimal therapy; Other CTCAE grade ≥3 toxicity which, in the opinion of the investigator, is CS and related to AZD8931; Delay to the administration of paclitaxel on D1 of Cycle 2 by ≥7 days. Patients could have more than one DLT. Measure:The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel Timepoints:Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression) Measure:Progression-free-survival (PFS) Were Analyzed in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone Timepoints:Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012 ; Outcome name:The number of subjects with at least one visit response of CR or PR (Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Not Evaluable (NE), All target lesion measurements are missing or >1/3 target lesion measurements are missing and sum of diameters of non-missing target lesions does not qualify for PD; Not applicable (NA), No target lesions are recorded at baseline)) Measure:Objective Tumour Response Rate (ORR) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone Timepoints:Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012 ; Outcome name:The time from the date of randomization until the date of death due to any cause. Measure:The Overall Survival (OS) Was Compared in Patients Treated With AZD8931 in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone Timepoints:Weekly visits for routine safety monitoring, accessed up to data cut off on 11th April 2012 | — |
Countries
Belgium, Bulgaria, Czech Republic, France, Hungary, Italy, Peru, Sweden, United Kindgdom
Contacts
Public ContactEdward Ramirez
ASTRAZENECA PERU S.A.
Outcome results
None listed