The purpose of this study is to assess the safety and tolerability of the investigational anticancer drug DCR-MYC. DCR-MYC is a novel synthetic double-stranded RNA in a stable lipid particle suspension that targets the oncogene MYC. MYC oncogene activation is important to the growth of many hematologic and solid tumor malignancies. In this study the Sponsor proposes to study DCR-MYC and its ability to inhibit MYC and thereby inhibit cancer cell growth.
In this first-in human study, DCR-MYC will be administered by 2 hour intravenous (IV) infusion, once weekly for 2 weeks followed by a rest week (3 weeks = 1 cycle), to patients with either solid tumor malignancies, multiple myeloma, or non-Hodgkins lymphoma that have not responded to previous treatment. The highest safe dose of DCR-MYC that can be administered will be identified. In addition, the pharmacokinetic (PK) profile, potential pharmacodynamic (PD) effects, as well as the antitumor activity of DCR-MYC will be evaluated. There will be 2 expansion cohorts at the maximum tolerated dose (MTD) (or highest safe dose identified for further study which may be lower): * Biopsy Cohort: 6 patients, tumor biopsies to be performed pre-dosing and Cycle 2/Day 11; same assessments as dose escalation cohorts * PNET Cohort: Up to 20 patients with pancreatic neuroendocrine tumors; same assessments as dose escalation cohorts, however fewer PD (cytokine) assessments and no PK assessments
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Dosing: 2 hour IV infusion on Day 1 and 8 of each 21 day cycle. Starting dose: 0.1mg/kg/dose Dose escalation: 100%, 50%, or 25% increase in subsequent cohorts depending upon toxicity. Number of cycles: until progression or unacceptable toxicity develops.
Stanford Cancer Institute
Stanford, California, United States
University of Chicago
Chicago, Illinois, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
South Texas Accelerated Research Therapeutics (START)-Midwest
Grand Rapids, Michigan, United States
MD Anderson Cancer Center
Houston, Texas, United States
South Texas Accelerated Research Therapeutics (START), LLC
San Antonio, Texas, United States
Number of patients with adverse events as a measure of safety and tolerability
Part A: 1 patient cohorts with 100% dose increase between cohorts until \>/= Grade 2 study drug-related toxicity during Cycle 1, then expand to 3 patients and move to Part B. Part B: 3 patient cohorts with 50% dose increase between cohorts until study drug-related DLT during Cycle 1, then expand to 6 patients and move to Part C. Part C: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation and expand previous MTD cohort to 18 patients.
Time frame: Cycle 1 (3 weeks), longer if DRC-MYC is continued; with 30 days follow-up after last dose
DCR-MYC levels in blood
Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11)
Time frame: Cycle 1; Week 1 and Week 2
DCR-MYC biological activities
Collection of blood samples for cytokine measurements Week 1 (Day 1, 2, and 4) and Week 2 (Day 8)
Time frame: Cycle 1; Week 1 and Week 2
DCR-MYC biological activities
PET imaging to be performed Cycle 1/Day 1, Cycle 1/Day 11, and End of Cycle 4
Time frame: Cycle 1, Cycle 2, and Cycle 4
DCR-MYC biological activities
Tumor biopsies (2 total) to be performed in MTD expansion cohort only. Patients will have biopsies performed prior to Cycle 1 and Cycle 2/Day 11
Time frame: Cycle 1 and Cycle 2
Preliminary antitumor activity
Evaluation for evidence of objective response or disease stabilization
Time frame: After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continued
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