Phase Ib/2, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Hepatocellular Carcinoma

NCT02314052 | Terminated Phase 1 Results

• 1 other identifier: DCR-MYC-102
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• 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

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability

  Part A: 3 patient cohorts with 50% dose increase between cohorts until study drug-related dose-limiting toxicity (DLT) during Cycle 1, then expand to 6 patients and move to Part B. Part B: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation. Expand MTD cohort to 12 patients; tumor biopsies to be performed in this Phase 1b MTD Biopsy Cohort (6 patients).

  Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose

• Phase 2: Patients With Adverse Events as a Measure of Safety and Tolerability

  Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); further evaluation of safety and tolerability.

  Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose

• Phase 2: Preliminary Antitumor Activity

  Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); evaluation for evidence of objective response or disease stabilization.

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

Secondary Outcomes (7)

• Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8

  Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4

• DCR-MYC Biological Activities (Phase 1b Only)

  Cycle 1; Week 1

• DCR-MYC Biological Activities (Phase 1b Only)

  Cycle 1 and 2

• Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8

  Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4

• Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8

  Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4

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: 0.125mg/kg/dose Number of cycles: until progression or unacceptable toxicity develops. PHASE 1b Dose escalation: 50% or 25% increase in subsequent cohorts depending upon toxicity until maximum tolerated dose (MTD) is identified. PHASE 2 Cohort expansion at the MTD: Additional patients to be treated at the highest dose tolerated to assess efficacy and further assess safety

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 (in Singapore \> 21 years or \> 18 years with consent of guardian).
• Patients with documented (histologically- or cytologically-proven) HCC, with at least 1 measureable lesion \> 10 mm (excluding bone metastases). If the measurable lesion(s) is in the liver, it either should not have been treated previously with loco-regional therapy, or there must be demonstrated progression of the lesion following previous loco-regional therapy.
• Patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
• Patients who are either refractory to or intolerant of sorafenib despite dose reduction and best supportive care, or patients who do not have access to sorafenib or other suitable therapy for HCC.
• Patients with underlying hepatic cirrhosis must have a current cirrhosis status of Child-Pugh Class A (i.e., score of 5-6) without encephalopathy.
• Phase 1b MTD Biopsy Cohort: Patients with primary or metastatic tumor site(s) considered safely accessible for biopsy and consenting to undergo pre- and post-dosing tumor biopsies.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, 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 mixed histology cholangiocarcinoma and HCC, or fibrolamellar variant HCC.
• Patients with any of the following hematologic abnormalities at baseline:
• Hemoglobin \< 8.5 g/dL
• Absolute neutrophil count \< 1,500 per mm3
• Platelet count \< 75,000 per mm
• Patients with any of the following serum chemistry abnormalities at baseline:
• Total bilirubin \> 1.5 × the upper limit of normal (ULN) for the institution
• AST or ALT \> 5 × the ULN for the institution
• Serum creatinine \> 1.5 × the ULN for the institution
• Patients with the following coagulation parameter abnormality at baseline:
• INR \> 1.7 × ULN for the institution
• Patients with:
• A history of deep vein thrombosis (DVT) or pulmonary embolism (PE), within 6 months prior to first study drug administration; patients receiving systemic anti-coagulation for prophylactic or therapeutic reasons

Sponsors & Collaborators

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

Study Sites (6)

Mayo Clinic

Scottsdale, Arizona, 85259-5499, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

National University Hospital of Singapore

Singapore, 119228, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

The study was prematurely discontinued by the Sponsor because of evolving data from a separate study.

Results Point of Contact

• Title: Ralf Rosskamp
• Organization: Dicerna Pharmaceuticals

rrosskamp@dicerna.com

617-621-8097

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: December 8, 2014
• First Posted: December 10, 2014
• Study Start: January 27, 2015
• Primary Completion: October 11, 2016
• Study Completion: October 11, 2016
• Last Updated: July 11, 2024
• Results First Posted: September 4, 2018

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2); US (3); KR (1)