| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with locally recurrent and/or metastatic breast cancer that express low levels of HER2 protein and who have not received a taxane based chemotherapy regimen for their locally recurrent and/or metastatic disease. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10057654 |
| E.1.2 | Term | Breast cancer female |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the progression free survival (PFS) in patients treated with AZD8931 in combination with paclitaxel versus paclitaxel alone. |
|
| E.2.2 | Secondary objectives of the trial |
| 1.To investigate whether there is any effect on the pharmacokinetics (PK) of AZD8931 and/or paclitaxel when co-administered 2.To investigate the safety and tolerability of AZD8931 in combination with paclitaxel 3.To compare the objective tumour response rate in patients treated with AZD8931 in combination with paclitaxel versus paclitaxel alone 4.To compare the overall survival (OS) in patients treated with AZD8931 in combination with paclitaxel versus paclitaxel alone |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Provision of signed, written informed consent
2.Age 18 years and older
3.Radiation therapy must be terminated at least 2 weeks prior to enrolment. Patients must have recovered from the toxic effects of prior therapy
4.Suitable for paclitaxel therapy
5.Life expectancy of more than 12 weeks
6.Females of non-childbearing status defined as one of the following criteria at screening: negative pregnancy test in women of childbearing potential- or women who are permanently or surgically sterilised (hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) or postmenopausal (over 50 years old and amenorrheic for 12 months following cessation of all exogenous hormonal treatments, or over 57 years old)
7.Not pregnant or breastfeeding if female and of child-bearing potential
8.Female patients of child-bearing potential willing to use an acceptable highly effective method of contraception during the study and for 3 months after the last dose of IP. 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.Haemoglobin ≥9 g/dL (5.59 mmol/L)
10.Adequate liver function defined as;
-serum bilirubin ≤2 x ULN in the absence of noted liver metastases,
-or ALT or AST ≤2.5 x ULN in the absence of noted liver metastases,
-or ALP ≤2.5 x ULN in the absence of noted liver metastases,
-or ALP, AST or ALT ≤5.0 x ULN if judged by the investigator to be related to liver metastases
11.International normalised ratio and activated partial thromboplastin time ≥1.2 x ULN
12.Adequate renal function as demonstrated by serum creatinine ≤1.5 ULN, or creatinine clearance ≥50 mL/min
13.Adequate bone marrow reserve as demonstrated by an absolute neutrophil count ≥1.5 x 109/L or platelet count ≥100 x 109/L
14.Serum potassium ≤5.5 mmol/L
15.Resting ECG with measurable QTc interval of ≤480 msec at 2 or more time points within a 24 hour period
16.Cardiac ejection fraction within institutional range of normal as measured by echocardiogram (or MUGA scan if an echocardiogram cannot be performed or is inconclusive)
17.Able to discontinue medication with agents designated as Class I Arizona risk for QT prolongation (see Appendix D).Agents designated as Class II Arizona risk for QT are allowed provided the patient has received these agents for at least 5 half-lives of the drug with no change in dose
18.Female patients with histologic or cytologic diagnosis of breast cancer with evidence of unresectable and/or locally recurrent and/ or metastatic disease. Lesions should not be amenable to surgery or radiation of curative intent
19.Patient with low HER2 expressing tumours and who are deemed ineligible for trastuzumab or lapatinib treatment |
|
| E.4 | Principal exclusion criteria |
1.Previously randomised to treatment in this study
2.Receipt of investigational drug within the 14 days or 5 half-lives, whichever is longer, of the first dose of randomised therapy (AZD8931 or matching placebo) or participated in a previous clinical study during the last 30 days prior to study entry
3.Known immunodeficiency syndrome
4.Patients not able to swallow and retain oral medication
5.Current disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs
6.Unresolved toxicity ≥CTC grade 2 related to previous anti-cancer therapy, except alopecia
7.Known uncontrolled or symptomatic angina, arrhythmias or congestive heart failure; evidence of transmural infarction on ECG, poorly controlled hypertension (systolic >180 mmHg or diastolic >100 mmHg), significant valvular disease or history of high risk dysrrhythmia (such as ventricular fibrillation or ventricular tachycardia [includes ventricular triplets])
8.Last dose of anticancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or tumour embolisation) more than 14 days prior to the first dose of treatment with IP If sufficient wash-out time has not occurred due to schedule or PK properties, a longer wash-out period will be required, as agreed by AZ and the investigator
9.Known hypersensitivity to AZD8931, its excipients, or drugs in its class (including oral tyrosine kinase inhibitors)
10.Known hypersensitivity to paclitaxel and/or its excipients
11.Receiving or unable to stop use within specified time period (see Appendix D) of medications or herbal supplements with known moderate or potent inhibitory effects on CYP3A4 or CYP2D6, or potent inducing effects on CYP3A4 or CYP2D6
12.Prior exposure to anthracyclines or mitoxantrone with cumulative exposure less than 360 mg/m2 for doxorubicin, 720 mg/m2 for epirubicin or 72 mg/m2 for mitoxantrone
13.Personal history or repeated unexplained episodes of syncope/dizziness
14.Medical diagnosis of acne rosacea, psoriasis, severe atopic eczema
15.Prior history of dry eye syndrome eyelid or eyelash abnormalities, clinically significant ocular surface disease, eye injury, corneal surgery or prior orbital irradiation
16.Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
17.Active or uncontrolled systemic disease which makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
18.Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or squamous cell carcinoma of the skin with no relapse in the past 5 years)
19.Symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteriods before and during the study as long as these were started at least 4 weeks prior to enrolment
20.Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent
21.Other concurrent condition which in the investigator�s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival (PFS) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Lo studio si concludera` all`uscita di tutte le pazienti dallo studio. Le pazienti continueranno lo tudio fino a progressione di malattia, comparsa di tossicita` intollerabile o presenza di uno dei criteri per l�interruzione dello studio. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
Print
