A phase 1b/2 randomised placebo controlled trial of fulvestrant +/- AZD5363 in postmenopausal women with advanced breast cancer previously treated with a third generation aromatase inhibitor.
Breast cancer cells which have the estrogen receptor (ER positive or ER+) are more likely to grow when estrogen is present in the bloodstream. This can be treated by drugs that interfere with the action of estrogen or the estrogen receptor. Examples of this include Tamoxifen, and the Aromatase Inhibitors (Anastrozole Letrozole and Exemestane). Although these drugs are often effective for a while, the cancer can frequently become resistant and the drugs stop working. Patients then require treatment with chemotherapy. In this trial, we are investigating whether we can reverse resistance to hormone therapy by adding an additional oral drug called AZD5363.
This is a targeted therapy that blocks the action of a cellular protein called Akt, which has been shown to cause resistance to hormone therapy. We will combine this drug with fulvestrant, another hormone therapy which is sometimes used alone in patients who have developed resistance to Aromatase Inhibitors, or Tamoxifen. Thus, patients entering the trial will have a known drug with proven efficacy and will also possibly receive the experimental drug which may enhance activity.
Two phase study
The study is divided into two phases. The first phase is now closed to recruitment; it involved a small number of patients to test if fulvestrant and AZD5363 could be combined in a safe manner (safety run in phase 1b). All patients received a standard dose of fulvestrant and the phase 1b was used to determine the dose of AZD5363 used in phase 2. The dose of AZD5363 determined to be safe for use in phase 2 was 400mg.
This is a randomised controlled phase 2 trial where half the patients will receive fulvestrant alone (plus a dummy drug - placebo) and half will receive a combination of the fulvestrant and AZD5363 at 400mg. This will involve a larger number of patients and will allow us to compare the anticancer activity of fulvestrant alone versus fulvestrant and AZD5363.
Investigating resistance to hormone therapy
This trial is investigating whether it is possible to reverse resistance to hormone therapy by adding an additional oral drug called AZD5363. This is a targeted therapy that blocks the action of a cellular protein called Akt, which has been shown to cause resistance to hormone therapy. This drug will be combined with fulvestrant, another hormone therapy which is sometimes used alone in patients who have developed resistance to Aromatase Inhibitors, or Tamoxifen.
9-12 for Phase 1b. Recruited 9; Phase 1b is now closed.
138 for Phase 2. Recruited 140; Phase 2 is closed to recruitment and currently in follow up.
The trial has specific eligibility criteria to select participants who might be treated safely and have a good chance of receiving benefit from the treatment.
The trial enrolled 140 participants, who were randomly assigned to receive either fulvestrant and AD5363 -now known as capivasertib- (n = 69) or fulvestrant and placebo (n = 71).
The analysis of the data collected from participants shows that the combination of AZD5363 (capivasertib) and fulvestrant works better for women with oestrogen receptor positive breast cancer. Women who had AZD5363 (capivasertib) and fulvestrant were alive with no signs of their cancer getting worse for over 10 months (10.3); by contrast, for women who had placebo and fulvestrant, their cancer started to grow again after less than 5 months (4.8).
|Start date||1 Jan 2014|
|End date||1 Feb 2017|