Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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)

Protocol: OSU-15170

Full Title

A Phase Ib, Proof of Mechanism, Open-Label Study of RO7070179, A Hypoxia-Inducible Factor 1A (HIF1A) mRNA Antagonist in Adult Subjects with Hepatocellular Carcinoma (HCC)

Purpose

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.

Are you eligible?

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.

Liver Cancer Gastrointestinal Cancers