Phase I/II Study of AZD2281 Given in Combination With Paclitaxel in Metastatic Triple Negative Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This is the first part of a 2-part study assessing the efficacy of AZD2281 in combination with paclitaxel in 1st or 2nd line treatment of patients with metastatic triple negative breast cancer. This first part (Phase I) is an open-label, intra patient dose finding study to establish the appropriate doses and schedule of paclitaxel and AZD2281 in combination, to be used in the randomized Phase II part. The safety and tolerability of AZD2281 in combination with paclitaxel will be explored. Approximately 10 patients per cohort from 4-5 countries will be enrolled in Phase I.

Official Title
-----------------
Phase I/II Randomised, Double- Blind, Multi-centre Study to Assess the Efficacy of AZD2281 When Given in Combination With Paclitaxel in the 1st or 2nd Line Treatment of Patients With Metastatic Triple Negative Breast Cancer.

Conditions
-----------------
Breast Cancer, Triple Negative Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: AZD2281
* Drug: Paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with histologically or cytologically diagnosed metastatic triple negative breast cancer (Oestrogen, progesterone and HER2 negative adenocarcinoma of the breast) Patients must have normal organ and bone marrow function, ECOG performance status of no more than 2 Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing. Exclusion Criteria: Any chemotherapy, radiotherapy (except for palliative reasons) or investigational product, within 2 weeks from the last dose prior to study entry (or longer period, depending on the agent used) Major surgery within 4 weeks of starting the study, and must have recovered from any effects of major surgery Patients requiring treatment with the following:certain antibiotic drugs, St.John's Wort, carbamazepine, phenobarbitone, phenytoin, and certain protease inhibitors/ non-nucleoside reverse transcriptase inhibitors used as components of HIV/AIDS treatment, Patients with second primary cancer; except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for at least 5 years.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>paclitaxel + AZD2281 | Drug: AZD2281<br>* Dose finding study to establish the appropriate dose of AZD2281<br>* Other names: Olaparib;Drug: Paclitaxel<br>* Intravenous infusion over 1 hour<br>* Other names: Taxol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Adverse Events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry, hematology, urinalysis |  | Physical examination/ ECG approximately monthly.Adverse Events, Vital signs, Haematology/ clinical chemistry, Urinalysis weekly throughout the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, triple negative, metastatic