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Carcinoma, HepatocellularPhase 1NCT02564614

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)

A Phase 1 study testing RO7070179 in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
RO7070179
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
7 sitesUnited States
Study dates
2 May 2016to 22 Jan 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites
  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Ohio State University

    Columbus, Ohio, 43210

  • Indiana University

    Indianapolis, Indiana, 46202

  • Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

    New York, New York, 10016

  • NYU Langone Medical Center; Bellevue Hospital

    New York, New York, 10016

  • Weill Cornell Medical College

    New York, New York, 10021

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

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)

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.

Being tested
RO7070179
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO7070179Drug

    Also called SPC2968/EZN-2968

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

Study groups in NCT02564614
Study groupRoleWhat they receive
RO7070179ExperimentalParticipants 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.
Receives: Drug: RO7070179

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Pre-dose (baseline) and Week 6

Secondary outcomes (17)
  1. Change From Baseline to Week 6 in hypoxia-inducible factor 1a (HIF1A) Tumor Concentrations

    Measured: Pre-dose (baseline) and Week 6

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

    Measured: Pre-dose (baseline) and Week 6

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

    Measured: Pre-dose (baseline) and Week 6

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

    Measured: Pre-dose (baseline) and Week 6

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

    Measured: Pre-dose (baseline) and Week 6

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

    Measured: Pre-dose (baseline) and Week 6

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

    Measured: 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)

    Measured: Every 12 weeks upto 24 Months

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

    Measured: Every 12 weeks upto 24 Months

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

    Measured: Every 12 weeks upto 24 Months

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

    Measured: Every 12 weeks upto 24 Months

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

    Measured: Every 12 weeks upto 24 Months

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

    Measured: Every 12 weeks upto 24 Months

  14. Maximum Observed Plasma Concentration (Cmax)

    Measured: pre- and post-dose at Week 1, Week 6

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

    Measured: 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)]

    Measured: pre- and post-dose at Week 1, Week 6

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

    Measured: pre- and post-dose at Week 1, Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2015 (estimated)
  2. Study start2 May 2016
  3. Primary completion22 Jan 2018
  4. Study completion22 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02564614
Sponsor's protocol ID
NP29700
Status last verified
Feb 2018
First submitted
28 Sep 2015
Last updated
15 Feb 2018
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO7070179 in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 6 in HIF1A mRNA Level in Tumor Tissue (time frame: Pre-dose (baseline) and Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2018.

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