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

NCT02110563 | Terminated Phase 1

• 1 other identifier: DCR-MYC-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• DCR-MYC levels in blood

  Cycle 1; Week 1 and Week 2

• DCR-MYC biological activities

  Cycle 1; Week 1 and Week 2

• DCR-MYC biological activities

  Cycle 1, Cycle 2, and Cycle 4

• DCR-MYC biological activities

  Cycle 1 and Cycle 2

• Preliminary antitumor activity

  After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continued

Study Arms (1)

DCR-MYC

EXPERIMENTAL

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

Interventions

DCR-MYC DRUG

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.

DCR-MYC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, \> 18 years of age at the time of obtaining informed consent.
• Patients with a documented solid tumor malignancy that is locally advanced or metastatic; patients with documented multiple myeloma or non-Hodgkin's lymphoma.
• Patients with a malignancy that is either refractory to standard therapy or for which no standard therapy is available.
• Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
• Dose escalation portion of study: Patients with measurable or non-measurable disease according to standard response criteria .
• MTD Biopsy Cohort ONLY: Patients with measurable disease with primary or metastatic tumor site(s) considered safely accessible for biopsy; patients must consent to undergo 2 tumor biopsies.
• MTD PNET Cohort ONLY: Patients with advanced (unresectable or metastatic), histologically-confirmed low or intermediate grade PNET according to the World Health Organization (WHO) 2010 classification. Patients with neuroendocrine tumors (e.g., gastrinoma, VIPoma) in whom a pancreatic or peripancreatic primary is strongly suspected are also eligible. Patients must also have:
• 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.
• Patients with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and an anticipated life expectancy of ≥ 3 months.
• 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.
• 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.

You may not qualify if:

• Women who are pregnant or lactating. Women of child-bearing potential (WOCBP), and fertile men with a WOCBP-partner not using and not willing to use a medically effective method of contraception.
• Patients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
• Patients with leukemia (any form) or myelodysplastic syndromes.
• MTD PNET Cohort ONLY: Patients with poorly differentiated, high grade (grade 3) neuroendocrine carcinoma, as well as patients with adenocarcinoid, goblet cell carcinoid, or small cell carcinoma, or PNET patients with a Ki-67 proliferation index \> 20 %.
• Patients with any of the following hematologic abnormalities at baseline:
• Absolute neutrophil count \< 1,500 per mm3
• Platelet count \< 100,000 per mm3
• 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
• 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
• Patients with:

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (6)

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

South Texas Accelerated Research Therapeutics (START)-Midwest

Grand Rapids, Michigan, 49503, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma, Non-Hodgkin; Neuroectodermal Tumors, Primitive

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2014
• First Posted: April 10, 2014
• Study Start: April 1, 2014
• Primary Completion: October 5, 2016
• Study Completion: November 3, 2016
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)