Randomized, Phase II Trial of AZD6244 Alone and AZD6244 Plus Temsirolimus for Soft-Tissue Sarcomas
I. Compare the progression-free survival of the MEK inhibitor, AZD6244 alone, and the
combination of AZD6244 and a mammalian target of rapamycin inhibitor (mTORi), temsirolimus
(CCI-779) in patients with recurrent metastatic or recurrent locally unresectable
I. Determine the rates of apoptosis, autophagy, and proliferation with AZD6244 alone, and in
combination with temsirolimus by immunohistochemistry in tumor and surrogate skin tissue
biopsies. (exploratory) II. Assess the activation status of protein kinase B (Akt), 5E-BP1,
eukaryotic translation initiation factor 4 gamma, 1 (eIF-4G), and ribosomal protein S6
kinase (S6K) in tumor biopsy samples and surrogate skin tissue biopsy samples.(exploratory)
III. Assess inhibition of activated mitogen-activated protein kinase 1/2 (ERK1/2) in
stimulated peripheral blood mononuclear cells. (exploratory) IV. Assess response by Choi
criteria. V. Compare the response rate and 4-month progression-free survival (PFS) rate in
patients treated with these regimens.
VI. Compare the response rate, 4-month PFS rate and toxicity of AZD6244 alone and in
combination with temsirolimus.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral MEK inhibitor AZD6244 twice daily on days 1-28 and temsirolimus
IV over 30-60 minutes on days 1, 8, 15, and 22.
ARM II: Patients receive MEK inhibitor AZD6244 as in arm I. Patients who experience disease
progression may cross over to arm I.
In both arms, courses repeat every 28 days in the absence of disease progression or
After completion of study therapy, patients are followed up for 30 days.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Up to 30 days
City of Hope Medical Center
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|City of Hope Medical Center||Duarte, California 91010|
|Tower Cancer Research Foundation||Beverly Hills, California 90211|
|University of Southern California||Los Angeles, California 90033|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|University of California Davis Phase 2 Consortium||Sacramento, California 95817|