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)

February 13, 2018 updated by: Hoffmann-La Roche

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10021
        • Weill Cornell Medical College
      • New York, New York, United States, 10016
        • Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
      • New York, New York, United States, 10016
        • NYU Langone Medical Center; Bellevue Hospital
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RO7070179
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
RO7070179 (13 mg/kg/week) will be administered as 2-hour IV infusion.
Other Names:
  • SPC2968/EZN-2968

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change From Baseline to Week 6 in HIF1A mRNA Level in Tumor Tissue
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Change From Baseline to Week 6 in hypoxia-inducible factor 1a (HIF1A) Tumor Concentrations
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6
Change From Baseline to Week 6 in HIF2 Tumor Concentrations
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6
Change From Baseline to Week 6 in Vascular Endothelial Growth Factor (VEGF) Tumor Concentrations
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6
Change From Baseline to Week 6 in Erythropoietin (EPO) Tumor Concentrations
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6
Change From Baseline to Week 6 in Prolyl 4 Hydroxylase Tumor Concentrations
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6
Change From Baseline to Week 6 in CD34/von Willebrand factor (VWF) Tumor Concentrations
Time Frame: Pre-dose (baseline) and Week 6
Pre-dose (baseline) and Week 6
Change in Blood Alpha-fetoprotein (AFP) Concentrations from Baseline
Time Frame: Week 1 and Week 4 for Cycle 1 and at Week 1 for subsequent treatment cycles
Week 1 and Week 4 for Cycle 1 and at Week 1 for subsequent treatment cycles
Time to Progression (TTP) According to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST)
Time Frame: Every 12 weeks upto 24 Months
Every 12 weeks upto 24 Months
Percentage of Participants With Complete Response (CR) and Partial Response (PR) According to RECIST and mRECIST
Time Frame: Every 12 weeks upto 24 Months
Every 12 weeks upto 24 Months
Duration of Response (DOR) According to RECIST and mRECIST
Time Frame: Every 12 weeks upto 24 Months
Every 12 weeks upto 24 Months
Progression Free Survival (PFS) According to RECIST and mRECIST
Time Frame: Every 12 weeks upto 24 Months
Every 12 weeks upto 24 Months
Overall Survival (OS) According to RECIST and mRECIST
Time Frame: Every 12 weeks upto 24 Months
Every 12 weeks upto 24 Months
Percentage of Participants With Tumor Growth According to RECIST and mRECIST
Time Frame: Every 12 weeks upto 24 Months
Every 12 weeks upto 24 Months
Maximum Observed Plasma Concentration (Cmax)
Time Frame: pre- and post-dose at Week 1, Week 6
pre- and post-dose at Week 1, Week 6
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: pre- and post-dose at Week 1, Week 6
pre- and post-dose at Week 1, Week 6
Area under the Concentration-Time Curve From Zero to 168 Hours [AUC (0-168 hours)]
Time Frame: pre- and post-dose at Week 1, Week 6
pre- and post-dose at Week 1, Week 6
Plasma Decay Half-Life (t1/2)
Time Frame: pre- and post-dose at Week 1, Week 6
pre- and post-dose at Week 1, Week 6

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

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 Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 2, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 22, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 22, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 28, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 1, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 15, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NP29700

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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