Ariad Pharmaceuticals Inc fka ARIA

[BTH]

EN.8 - A PHASE III STUDY OF STANDARD THERAPY VERSUS RIDAFOROLIMUS IN WOMEN WITH RECURRENT OR METASTATIC ENDOMETRIAL CANCER WHO HAVE PREVIOUS HAD CHEMOTHERAPY

(this is in powerpoint presentation - this is the best it is presented online here):

http://webcache.googleusercontent.com/search?q=cache:BqYS5GdQotMJ:www.gcig.igcs.org/files/EN8Oza.ppt+endometrial+cancer+ridaforolimus&cd=12&hl=en&ct=clnk&gl=us&client=firefox-a


Looks like NCIC (Canada) is planning a larger trial (Phase 2 or 3) for endometrial cancer:

Proposed Design Change
Schema
Eligibility
Metastatic or recurrent endometrial cancer, not curable by other means
Patient with endometrial carcinoma for whom a hormonal therapy or chemotherapy would be considered an acceptable treatment option.
At least one prior chemotherapy and up to two prior chemotherapy regimens (chemotherapy may have been administered in the adjuvant OR for metastatic disease settings).
Measurable or non-measurable disease (per RECIST) site of disease
ECOG Performance status 0-2

mTOR in Endometrial Ca
NCIC CTG IND.192 Phase II Trial Update
Dose Intensity
Stratification
Patients will be stratified by:
Cooperative group
Performance status
Prior chemotherapy
Hormone receptor (ER/PR) status
Tumour grade
Proposed treatment (chemo versus hormones)
Endpoints
Primary Endpoint:
Overall survival
Secondary Endpoints:
Response rates
Duration of response
Time to progression
Toxicity
Quality of Life
Economic Analysis
Correlative Studies:
To explore potential prognostic and predictive factors in correlative studies of archival endometrial tissue.

Statistics
The primary endpoint of the study is overall survival.
We assume that the median overall survival for patients with prior chemotherapy treated with hormones is 8 months and the hazard ratio of ridaforolimus to hormones will be 0.75 (an improvement of 2.7 months in median survival); a two-sided alpha 0.05; and 80% power, then 380 deaths will be required.
Sample Size and Duration of Study
Accrual rate duration of follow-up sample size total duration
150 per year 12 months 450 4.0 years
200 per year 12 months 460 3.3 years
Translational Research
Formalin-fixed paraffin embedded blocks and one plasma blood sample will be obtained from patients entered into EN.8 phase 3 trials.
These samples will be analyzed for genetic abnormalities likely to correlate with benefit/resistance to mTOR inhibitor. The genetic profile will be determined through translational research studies undertaken concurrent with the proposed phase 3 trials.
The studies will evaluate the following:
One hundred snap frozen endometrial carcinoma specimens with associated blood samples will be obtained from the Ontario Tumour Bank. DNA will be extracted and assessed for amplifications and deletions. 100 samples will identify genetic events occurring at > 3%.
DNA from formalin fixed paraffin embedded samples obtained from NCIC CTG phase 2 studies of mTOR inhibitors will be extracted and analyzed for deletions and amplifcations identified from study 1. DNA results will be correlated with clinical outcomes of patients entered into the phase 2 trials to determine the genetic abnormalities that correlate with patient outcome.
The genetic profile will be tested on tumour samples and germline DNA obtained from patients enrolled on EN.8 study.
Status
Company and NCIC CTG phase II trials underway
Accrual slower than expected; both protocols amended to allow 1 prior chemotherapy
Company trial – RP2 - amended to allow chemotherapy OR hormonal agent in control arm
Projected completion of accrual April 2010 and analysis around ASCO
Potential to look at accrual rate and efficacy patients versus hormone or dealers choice control
Concept updated for potential international group collaborators
First draft of protocol completed – internal review prior to distribution to company and collaborators
Questions