Phase II Trial of mTOR Inhibitor Temsirolimus Combined With MEK Inhibitor AZD 6244 in Patients With BRAF Mutant Stage IV Melanoma
I. To determine the clinical response rate according to Response Evaluation Criteria in
Solid Tumors (RECIST) and one-year overall survival to the study drugs temsirolimus and
AZD6244 (selumetinib) hydrogen sulfate in BRAF V600E mutant unresectable stage IV melanoma.
I. Estimate 6-month progression-free survival in patients receiving temsirolimus and AZD6244
II. Determine the pharmacodynamic effects of temsirolimus and AZD6244 on pERK, s6K, PTEN and
mediators of apoptosis.
III. Determine the toxicity profile of temsirolimus with AZD6244 hydrogen sulfate.
Treatment Phase: This period began with the first intravenous (through the vein) infusion of
TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will
continue until Week 8 (Visit 4).
Investigators planned to have as many as 38 patients receive the same dosage of TEMSIROLIMUS
injected in the veins once a week for 8 weeks, and the AZD6244 was to be given as capsules
by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 was given
to participants as an outpatient, unless admission to the hospital was needed for treatment
of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and
AZD6244 was given every 8 weeks. The TEMSIROLIMUS was injected in a vein over 30 minutes.
The continuation phase was to begin with visits at weeks 12 in patients who receive at least
two cycles of treatments.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Complete Response (CR) and Partial Response (PR)
Anti-tumor response (CR+PR) was defined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|