A Study of Hypoxia-inducible Factor 1a (HIF1A) Messenger Ribonucleic Acid (mRNA) Antagonist (RO7070179), to Demonstrate Proof-of-mechanism in Adult Participants With Hepatocellular Carcinoma (HCC)

NCT02564614 | Completed Phase 1

• 1 other identifier: NP29700
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 7

Brief Summary

This open-label study will demonstrate proof-of-mechanism of HIF1A inhibition by a decrease of HIF1A mRNA after intravenous (IV) infusion of RO7070179 in participants with hepatocellular carcinoma (HCC) who have failed at least one line of systemic therapy. This will be a single arm study and all participants will receive RO7070179, 13 milligram per kilogram per week (mg/kg/week), 2-hour IV infusion on Days 1 and 4 during Week 1 of Cycle 1, followed by once weekly in 6 week cycle. Treatment with RO7070179 will be continued until disease progression or unacceptable toxicity.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 6 in HIF1A mRNA Level in Tumor Tissue

  Pre-dose (baseline) and Week 6

Secondary Outcomes (17)

• Change From Baseline to Week 6 in hypoxia-inducible factor 1a (HIF1A) Tumor Concentrations

  Pre-dose (baseline) and Week 6

• Change From Baseline to Week 6 in HIF2 Tumor Concentrations

  Pre-dose (baseline) and Week 6

• Change From Baseline to Week 6 in Vascular Endothelial Growth Factor (VEGF) Tumor Concentrations

  Pre-dose (baseline) and Week 6

• Change From Baseline to Week 6 in Erythropoietin (EPO) Tumor Concentrations

  Pre-dose (baseline) and Week 6

• Change From Baseline to Week 6 in Prolyl 4 Hydroxylase Tumor Concentrations

  Pre-dose (baseline) and Week 6

Study Arms (1)

RO7070179

EXPERIMENTAL

Participants will receive RO7070179, 13 mg/kg/week, 2-hour IV infusion every week in a 6-week cycle, after two loading doses in Week 1 of Cycle 1 on Day 1 and Day 4. If a dose-limiting toxicity (DLT) occurs in more than 33% of participants at any time, the dose will be reduced to 10 mg/kg/week. The dose will be further reduced to 6 mg/kg/week if more than 33% of treated participants have a DLT.

Drug: RO7070179

Interventions

RO7070179 DRUG

RO7070179 (13 mg/kg/week) will be administered as 2-hour IV infusion.

Also known as: SPC2968/EZN-2968

RO7070179

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 of \>=18 years of age with the Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Child-Pugh score of 5-7, and Life expectancy of 3 months or greater.
• Confirmed to have HCC as described by the American Association for the Study of Liver Disease (AASLD).
• Participants who have failed at least one line of systemic therapy for advanced stage HCC or participants who are ineligible or unable to tolerate the standard of care treatment.
• Have measurable or evaluable disease.
• Participants with normal major organ functions as defined by hemoglobin (HgB) \>= 8.5 gram/decilitre (dL), absolute neutrophil count (ANC) \>= 1000/microliter (mcL), platelet \>= 60,000/micL, aspartate aminotransferase/alanine transaminase (AST/ALT) \<= 3 x Upper Limit of Normal (ULN), total Bilirubin \<= 2 x ULN, creatinine \<= 2 x ULN.
• Willingness to undergo two tumor biopsies: before and after administration of RO7070179.

You may not qualify if:

• Active hepatitis B or C, but participants on stable medications for hepatitis B or C.
• Bleeding esophageal or gastric varices within 2 months before enrollment.
• Participants who need to take therapeutic anti-coagulation or anti-platelet therapy.
• Presence of ascites that preclude biopsy of liver lesions.
• History of unstable angina or myocardial infarction within 12 months prior to Day 1 or ischemic heart disease.
• Known HIV positive and positive screening pregnancy test or is breast-feeding.
• Female or male of reproductive capacity unwilling to use methods of contraception to prevent pregnancy during this study. Participants unwilling to use methods of contraception to prevent pregnancy for 6 months after the last dose of RO7070179 due to the potential for prolonged half-life of RO7070179 in the liver.
• Known, clinically suspected, or history of CNS tumor involvement.
• Prior chemotherapy, immunotherapy, investigational therapeutic agent, or other therapy used to treat HCC within 4 weeks before the first scheduled administration of RO7070179.
• Participants who have not recovered from any reversible side effects (except alopecia) to Grade 0 or 1 toxicity attributed to the administration of an investigational therapeutic agent, chemotherapy, immunotherapy, radiotherapy, or other agents previously used to treat the cancer.
• Any condition that, in the opinion of the investigator or the Sponsor, makes the patients unsuitable for the study.
• Inability to comply with the study protocol.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, 10016, United States

Location

NYU Langone Medical Center; Bellevue Hospital

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

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: September 28, 2015
• First Posted: October 1, 2015
• Study Start: May 2, 2016
• Primary Completion: January 22, 2018
• Study Completion: January 22, 2018
• Last Updated: February 15, 2018

Record last verified: 2018-02

Locations

US (7)