Phase I, Multicenter, Dose Escalation Study Of DCR-MYC In Patients With Solid Tumors, Multiple Myeloma, Or Lymphoma

Study Overview

Phase I, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Solid Tumors, Multiple Myeloma, or Lymphoma

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

Solid Tumors
Multiple Myeloma
Non-Hodgkins Lymphoma
Pancreatic Neuroendocrine Tumors
PNET
NHL

DRUG: DCR-MYC

DCR-MYC-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-04-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-07-10
First Submitted that Met QC Criteria 2014-04-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-07-11
First Posted (ACTUAL) 2014-04-10	Results First Posted N/A	Last Verified 2024-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: DCR-MYC Patient groups (cohorts) will receive a single dose level of DCR-MYC; the dose level of DCR-MYC will be increased in subsequent cohorts	DRUG: DCR-MYC 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 develop

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: DCR-MYC

Patient groups (cohorts) will receive a single dose level of DCR-MYC; the dose level of DCR-MYC will be increased in subsequent cohorts

DRUG: DCR-MYC

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 develop

Primary Outcome Measures	Measure Description	Time Frame
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.	Cycle 1 (3 weeks), longer if DRC-MYC is continued; with 30 days follow-up after last dose

Secondary Outcome Measures	Measure Description	Time Frame
DCR-MYC levels in blood	Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11)	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)	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	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	Cycle 1 and Cycle 2
Preliminary antitumor activity	Evaluation for evidence of objective response or disease stabilization	After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continued

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

A Ki-67 proliferation index < 20%
Demonstrated radiological evidence of disease progression during or following the last treatment regimen (based on CT, MRI, or Octreoscan®)
Measurable disease according to RECIST v1.1 (determined by CT or MRI). Any lesions which have been subjected to percutaneous therapies or radiotherapy should not be considered measureable, unless the lesion has clearly progressed (per RECIST v1.1) since the procedure.
Received < 2 prior systemic treatments for PNET, at least one of which must have been an FDA-approved targeted therapy for PNET (i.e., sunitinib [Sutent®] or everolimus [Afinitor®]). Treatment with a somatostatin analog (SSA) will not be considered as a systemic treatment for the purposes of eligibility. 8. Patients with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and an anticipated life expectancy of ≥ 3 months. 9. Patients, both male and female, who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and for 3 months after the last dose of study drug. 10. Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.

Absolute neutrophil count < 1,500 per mm3
Platelet count < 100,000 per mm3 6. Patients with any of the following serum chemistry abnormalities at baseline:

Total bilirubin > 1.5 × the ULN for the institution
AST or ALT > 3 × the ULN for the institution (> 5 × if due to hepatic involvement by tumor)
Creatinine > 1.5 × ULN for the institution 7. Patients with any of the following coagulation parameter abnormalities at baseline:

PT (INR) > 1.5 × ULN for the institution
PTT > 1.5 × ULN for the institution 8. Patients with:

Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 6 months prior to first study drug administration; patients receiving systemic anti-coagulation for prophylactic or therapeutic reasons
Active uncontrolled bleeding or a known bleeding diathesis 9. Patients with a significant cardiovascular disease or condition, including:

Congestive heart failure currently requiring therapy
Need for antiarrhythmic medical therapy for a ventricular arrhythmia
Severe conduction disturbance (e.g., 3rd degree heart block)
Angina pectoris requiring therapy
Known left ventricular ejection fraction < 50% by MUGA or echocardiogram
QTc interval > 450 msec in males, or > 470 msec in females
Uncontrolled hypertension (per the Investigator's discretion)
Class III or IV cardiovascular disease according to the New York Heart Association's Functional Criteria.
Myocardial infarction within 6 months prior to first study drug administration 10. Patients with a known or suspected hypersensitivity to any of the components of lipid nanoparticle-formulated DCR-MYC. 11. Patients with a known history of human immunodeficiency virus or active infection with hepatitis B virus or hepatitis C virus. 12. Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first study drug administration. 13. Patients with inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy. 14. Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to first study drug administration. 15. Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug. 16. Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study-related evaluations. 17. Patients with the inability or with foreseeable incapacity, in the opinion of the Investigator, to comply with the protocol requirements.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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