| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
| The main objective of this trial is to establish whether the addition of ZD4054 to carboplatin is an active regimen in metastatic breast cancer in terms of progression-free survival. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives of this trial are to determine if the combination of ZD4054 and carboplatin is safe, feasible and tolerable in this patient population and to collect blood and tissue samples from this patient population to facilitate future translational research. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Participants will be asked to participate in an optional sub-study of the main trial which is detailed in section 13 PLANET Translational sub-study research of the trial protocol supplied with this application (version number 1.0). All PLANET participants will be asked to consider the provision of additional blood samples for translational research. A separate research proposal will be submitted to fund analysis of collected samples. These samples will be collected pre- and post-treatment at baseline and week 18. Permission will also be sought to analyse paraffin tissue blocks of diagnostic tumour tissue specimens. The objective of the sub-study is to analyse these samples to gain a better understanding of the carboplatin and ZD4054 treatment combination in metastatic breast cancer. |
|
| E.3 | Principal inclusion criteria |
The main inclusion criteria for this trial are as follows:
1) Patients aged over 18 years
2) Histological or cytological diagnosis of metastatic breast cancer, or previous histological diagnosis of breast cancer and evidence of metastatic or locally advanced disease unsuitable for local therapy.
3) No more than 2 prior lines of chemotherapy treatment for metastatic breast cancer.
4) Life expectancy greater than 3 months
5) Patients must have previously received or be ineligible for a taxane
6) Informed consent
7) Adequate bone marrow and hepatic function.
8) Haemoglobin ≥ 9.0 g/dl (if no prior transfusion or transfusion more than 4 weeks previously) or ≥ 10.0 g/dl (transfusion within last 4 weeks), absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L;
9) Total bilirubin < 1.5 x upper normal limit;
10) AST and ALT ≤ 2.5 x upper normal limit (or ≤ 5x UNL in the presence of liver metastases);
11) Adequate renal function.
12) GFR ≥60mls/min calculated using Wright Formula or measured by EDTA plasma clearance (See 10.1 and Appendix 3).
13) At least one measurable lesion on CT scanning. Disease measurable by other RECIST v1.1 compatible imaging (e.g. MRI, CXR) or clinically measurable will be allowed as long as the same assessment method is used throughout the trial.
14) ECOG performance status ≤2. |
|
| E.4 | Principal exclusion criteria |
The main exclusion criteria for this trial are as follows:
1) Previous treatment with platinum based chemotherapy.
2) Previous treatment with ZD4054.
3) Co-existing active infection or serious concurrent medical condition.
4) Significant cardiovascular disease defined as:
•history of congestive heart failure requiring therapy (NHYA grade 2 or higher);
•history of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry;
•presence of severe valvular heart disease;
•presence of a ventricular arrhythmia requiring treatment.
5) Any co-existing medical condition that, in the investigator’s judgement, may substantially increase the risk associated with the patient’s participation in the study or potentially hamper compliance with the study protocol and follow-up schedule.
6) Known brain or leptomeningeal metastases.
7) Gastrointestinal disorders likely to interfere with absorption of the study drug.
8) Patients known to be serologically positive for Hepatitis B or Hepatitis C (mandatory testing not required).
9) Immunocompromised patients e.g. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) (mandatory testing not required).
10) Participation in any other interventional clinical study within the previous 4 weeks or during the course of this study.
11) Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol.
12) Other previous or current malignant disease likely to interfere with protocol treatment or comparisons.
13) Concomitant administration of potent CYP3A inhibitors, specifically: Protease inhibitors (atanazavir, indinavir, nelfinavir, ritonavir, saquinavir), Macrolide antibiotics (clarithromycin, telithromycin), Azole antifungals (ketoconazole, itraconazole, voriconazole), nefazodone.
14) Concomitant administration of CYP3A inducers, specifically: rifampicin, rifapentine, rifabutin, phenytoin, carbamazepine, phenobarbitol, St John’s Wort. See section 8.5.1.
15) Women who are breastfeeding |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-Free Survival(PFS). Progression is defined according to RECIST 1.1. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| For the purposes of complying with UK Medicines for Human Use (Clinical Trial) Regulations introduced in May 2004, the trial will be considered closed when the last participant has completed protocol treatment. However, further observational follow up will continue for a minimum of one year. For the purposes of Research Ethics Committee approval, the study date is deemed to be the date of last data capture. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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