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Completed

NCT Number: NCT02564614

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)

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Indiana University, Indianapolis, Indiana, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

RO7070179

Drug

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

Other names: SPC2968/EZN-2968

Primary outcomes

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

    Time frame: Pre-dose (baseline) and Week 6

Secondary outcomes

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

    Time frame: Pre-dose (baseline) and Week 6

  2. Change From Baseline to Week 6 in HIF2 Tumor Concentrations

    Time frame: Pre-dose (baseline) and Week 6

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

    Time frame: Pre-dose (baseline) and Week 6

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

    Time frame: Pre-dose (baseline) and Week 6

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

    Time frame: Pre-dose (baseline) and Week 6

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

    Time frame: Pre-dose (baseline) and Week 6

  7. 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

  8. 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

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

    Time frame: Every 12 weeks upto 24 Months

  10. Duration of Response (DOR) According to RECIST and mRECIST

    Time frame: Every 12 weeks upto 24 Months

  11. Progression Free Survival (PFS) According to RECIST and mRECIST

    Time frame: Every 12 weeks upto 24 Months

  12. Overall Survival (OS) According to RECIST and mRECIST

    Time frame: Every 12 weeks upto 24 Months

  13. Percentage of Participants With Tumor Growth According to RECIST and mRECIST

    Time frame: Every 12 weeks upto 24 Months

  14. Maximum Observed Plasma Concentration (Cmax)

    Time frame: pre- and post-dose at Week 1, Week 6

  15. Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Time frame: pre- and post-dose at Week 1, Week 6

  16. 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

  17. Plasma Decay Half-Life (t1/2)

    Time frame: pre- and post-dose at Week 1, Week 6

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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)

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Oct 1, 2015
Registry last updated
Feb 15, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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