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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)

Primary Purpose

Carcinoma, Hepatocellular

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RO7070179

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

Concurrent serious medical illness that could potentially interfere with protocol compliance (such medical illness will not include hepatitis or cirrhosis, as the degree of liver impairment caused by these diseases are covered by other exclusion criteria).
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.

Sites / Locations

Indiana University
Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
NYU Langone Medical Center; Bellevue Hospital
Weill Cornell Medical College
Columbia University Medical Center
Gabrail Cancer Center
Ohio State University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RO7070179

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Change From Baseline to Week 6 in HIF2 Tumor Concentrations

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

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

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

Change From Baseline to Week 6 in CD34/von Willebrand factor (VWF) Tumor Concentrations

Change in Blood Alpha-fetoprotein (AFP) Concentrations from Baseline

Time to Progression (TTP) According to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST)

Percentage of Participants With Complete Response (CR) and Partial Response (PR) According to RECIST and mRECIST

Duration of Response (DOR) According to RECIST and mRECIST

Progression Free Survival (PFS) According to RECIST and mRECIST

Overall Survival (OS) According to RECIST and mRECIST

Percentage of Participants With Tumor Growth According to RECIST and mRECIST

Maximum Observed Plasma Concentration (Cmax)

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Area under the Concentration-Time Curve From Zero to 168 Hours [AUC (0-168 hours)]

Plasma Decay Half-Life (t1/2)

Full Information

NCT ID

NCT02564614

First Posted

September 28, 2015

Last Updated

February 13, 2018

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT02564614

Brief Title

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)

Official Title

A Phase 1b, Proof of Mechanism, Open-label Study of RO7070179, a Hypoxia-inducible Factor 1a (HIF1A) mRNA Antagonist in Adult Subjects With Hepatocellular Carcinoma (HCC)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

May 2, 2016 (undefined)

Primary Completion Date

January 22, 2018 (Actual)

Study Completion Date

January 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Hepatocellular

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RO7070179

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

RO7070179

Other Intervention Name(s)

SPC2968/EZN-2968

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame