The main purpose of the study is to establish an optimal and safe dose of AZD5363 when combined with paclitaxel. It will also indicate whether AZD5363, in combination with paclitaxel, has an effect on the type of breast cancer that you have. This…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A: To assess the safety and tolerability of two schedules of AZD5363
(continuous and intermittent dosing) when combined with weekly paclitaxel in
patients with advanced or metastatic breast cancer; and to recommend, by
assessment of dose limiting toxicities and other safety, tolerability,
pharmacokinetic and pharmacodynamic data, a dose and schedule of AZD5363 for
further study when combined with weekly paclitaxel.
Part B: To assess the relative anti-tumour activity of AZD5363 when combined
with weekly paclitaxel vs. weekly paclitaxel plus placebo by comparison of
change in tumour size at 12 weeks (target lesion assessment using RECIST 1.1)
in the overall advanced or metastatic Estrogen Receptor positive breast cancer
population and in a Phosphoinositide 3-kinase (PIK3CA) mutation-positive
sub-population.
Secondary outcome
Part A: To make a preliminary assessment of the anti-tumour activity of AZD5363
when combined with paclitaxel.
Part B:
* To assess the relative efficacy of AZD5363 when combined with weekly
paclitaxel compared with weekly paclitaxel plus placebo.
* To assess the safety and tolerability of AZD5363 when combined with weekly
paclitaxel compared with weekly paclitaxel plus placebo.
* To investigate the effect on patients* quality of life of AZD5363 when
combined with weekly paclitaxel, compared with weekly paclitaxel plus placebo.
Parts A and B:
* To assess the pharmacokinetics of AZD5363 when combined with paclitaxel.
*To assess the pharmacokinetics of paclitaxel alone and when combined with
AZD5363.
* To assess the pharmacokinetic/pharmacodynamic relationship.
Background summary
For many types of cancer there is an urgent need for new treatments. AZD5363
is a new anti cancer treatment that inhibits the kinase activity of AKT (also
known as protein kinase B). AZD5363 acts on cancers by blocking signalling
throught the AKT cellular survival pathway, leading to inhibition of cell
proliferation and increased apoptosis.
In this study AZD5363 is used in combination with paclitaxel. The standard
chemotherapy agent, paclitaxel, is given to destroy cancer cells. AZD5363 may
slow down tumor growth and may also make the cancer more sensitive to
paclitaxel and so make this agent more effective.
The main purpose of the study is to establish an optimal and safe dose of
AZD5363 when combined with paclitaxel. It will also indicate whether AZD5363,
in combination with paclitaxel, has an effect on the type of breast cancer that
you have. This study will also look at the relationship between tumours with
PIK3CA mutations and the effect of the treatment. In tumours with this so
called PIK3CA mutation the response to AZD5363 may be better. PIK3CA mutations
are found commonly in breast cancers.
The information gathered from this study is important for the further
development of this substance and the treatment of future subjects with this
substance.
Study objective
The main purpose of the study is to establish an optimal and safe dose of
AZD5363 when combined with paclitaxel. It will also indicate whether AZD5363,
in combination with paclitaxel, has an effect on the type of breast cancer that
you have. This study will also look at the relationship between tumours with
PIK3CA mutations and the effect of the treatment. In tumours with this so
called PIK3CA mutation the response to AZD5363 may be better. PIK3CA mutations
are found commonly in breast cancers.
Study design
This study will be conducted in two parts:
Part A = safety run-in with AZD5363 + paclitaxel (dosis escalation)
Part B = a randomised expansion with AZD5363 + paclitaxel versus paclitaxel +
placebo
The study design is:
* international
* multicentre
* open-label (Part A only)
* double-blinded (Part B only)
* randomised (Part B only)
* placebo-controlled (Part B only)
* stratified (Part B only)
Intervention
Part A: Cycles of 4 weeks in which a weekly infusion of paclitaxel is
administered during the first 3 weeks. AZD5363 capsules are taken twice daily
according to a continuous or intermittent dosing scheme.
Part B: Cycles of 4 weeks in which a weekly infusion of paclitaxel is
administered during the first 3 weeks. AZD5363/placebo capsules are taken twice
daily according to the dosing scheme established in Part A.
Study burden and risks
On several days during the study patients will undergo the following
assessments:
-CT or MRI scan
-physical examination
-vital signs (blood pressure, pulse)
-lenght
-weight
-ECG
-blood and urine assessments
-MUGA/echocardiogram
-blood and urine testing
-tumour biopsy (optional)
-collection of hairfollicles (eyebrows)
-pregnancy testsing
The following side effects are reported or may be expected:
-changes in glucose and insulin levels (high bloodsugar levels)
-diarrhea
-skin rash
-changes in strenght of heartbeat and blood pressure
-changes in liver function
- changes in pituitary, thyroid and adrenal glands as well as in the
reproductive tract
Female patients must not become pregnant during the study.
Louis Pasteurlaan 5
Zoetermeer 2719 EE
NL
Louis Pasteurlaan 5
Zoetermeer 2719 EE
NL
Listed location countries
Age
Inclusion criteria
* Provision of informed consent
* Female patients
* Aged at least 18 years
* Histological or cytological confirmation of breast cancer with evidence of advanced or metastatic disease (must be ER+ve in Part B)
* World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks
* Minimum life expectancy of 12 weeks
Exclusion criteria
* Clinically significant abnormalities of glucose metabolism;* Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids);* Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV;* Any prior exposure to agents which inhibit AKT as the primary phamacological activity;Part A: more than two prior courses of chemotherapy (including taxanes) for advanced or metastatic breast cancer.;Part B: any prior chemotherapy for advanced or metastatic breast cancer.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-006312-31-NL |
| ClinicalTrials.gov | NCTnummernognietbekend. |
| CCMO | NL40149.031.12 |