The purpose of this study is to find out how often two investigational drugs that are given together will shrink the patient's tumor and how well they will prolong the time it takes their tumor to grow. The investigators also wish to find out how they affect certain substances in the patient's tumor and in their blood important for tumor growth. The combination of these drugs is experimental, and has not been proven to help treat melanoma
PRIMARY OBJECTIVES: I. To determine the clinical response rate (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. SECONDARY OBJECTIVES: I. Estimate 6-month progression-free survival in patients receiving temsirolimus and AZD6244 hydrogen sulfate. 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. OUTLINE: Treatment Phase: This period begins 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). As many as 38 patients will receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 will be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 will be 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 will be given every 8 weeks. The TEMSIROLIMUS will be injected in a vein over 30 minutes. The continuation phase begins with visits at weeks 12 in patients who receive at least two cycles of treatments.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
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.
Time frame: 1 year
Number of Participants With Overall Survival (OS) at One Year
The one-year overall survival of the combination of temsirolimus and AZD6244 Hydrogen Sulfate.
Time frame: 1 year post last treatment
Number of Participants With Progression Free Survival (PFS) at 6 Months.
Patients will be evaluated by physical examination and imaging assessments (brain MRI and CT scans of the chest, abdomen and pelvis). Disease progression will be defined by RECIST criteria on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: 6 months from day 1 of treatment
Number of Participants With Related Serious Adverse Events (SAEs)
Toxicities assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.
Time frame: 1 year
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