CVM-1118 and Sorafenib Combination in Subjects With Advanced Hepatocellular Carcinoma

Conditions:Liver Cancer, Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:July 12, 2018
End Date:June 2021
Contact:Kirsten Dorr, IMBA

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A Phase 2, Open-Label Study With Orally Administered CVM-1118 and Sorafenib in Subjects With Advanced Hepatocellular Carcinoma

CVM-1118 is a new small molecule chemical entity being developed as a potential anti-cancer
therapeutic by TaiRx, Inc. CVM-1118 is a potent anti-cancer agent in numerous human cancer
cell lines. The safety of administrating CVM-1118 on human is evaluated from the phase 1
study. The objectives of the phase 2 study is to further investigate the efficacy of CVM-1118
with sorafenib for subjects with advanced hepatoma.

Sorafenib is a multi-kinase inhibitor that inhibits tumor growth and angiogenesis. Although
sorafenib is the first-line treatment of advanced hepatocellular cancer (HCC), patients
developing resistance to sorafenib have been reported.

To meet the medical need, TaiRx, Inc. develops a new small molecule drug, CVM-1118 targeting
the formation of vasculogenic mimicry (VM). VM has been associated with tumor metastasis and
poor clinical outcomes. VM is reported to be particularly active in tumor under hypoxia state
when patients are treated with the potent vascular endothelial growth factor (VEGF) inhibitor
like sorafenib. Hence, the ability of inhibiting the VM network make CVM-1118 a potential
good combination drug with sorafenib for advanced diseases.

The safety profile of CVM-1118 dosing has been established in the phase 1 study. The analysis
of metabolism pathways further showed that the potential of CVM-1118 and sorafenib drug-drug
interactions are very low.

Based on the mechanism of actions and the safety analysis of sorafenib and CVM-1118, the
design of phase 2 trial with the combination therapy might have great potential for the
patients with advanced HCC.

Inclusion Criteria:

1. Signed, informed consent

2. Age 18 or older (for all treatment locations with exception of Taiwan), or age 20 or
older (Taiwan only)

3. Pathologically or cytologically-confirmed, advanced-stage hepatocellular carcinoma
without prior systemic treatment and Child-Pugh liver function class A appropriate for
treatment with sorafenib

4. Measurable disease according to modified Response Evaluation Criteria in Solid Tumors
criteria (mRECIST)

5. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1

6. Adequate laboratory parameters including:

1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3.0 x
upper limit of normal (ULN), or AST and ALT ≤ 5.0 x ULN if liver function
abnormalities are due to underlying malignancy

2. Total serum bilirubin ≤ 2.0 x ULN (except for subjects with documented Gilbert's
syndrome who have a limit of ≤ 3.0 x ULN)

3. Absolute neutrophil count (ANC):1500/µL

4. Platelets: 90,000/µL

5. Hemoglobin: 9.0 g/dL

6. Serum creatinine ≤ 2.0 x ULN or creatinine clearance of ≥ 50 mL/min

7. Serum albumin ≥ 3.0 g/dL

8. International normalized ratio (INR) ≤ 1.4

9. Prothrombin Time (PT)/ Activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x ULN

7. QTc interval (using Fridericia correction) of ≤ 470 msec (QTc interval may be derived
from up to 3 separate EKGs performed at least 5 minutes apart)

8. Willingness to participate in collection of pharmacokinetic and other exploratory
blood collection as defined in the protocol

9. Willingness to use adequate contraception throughout study and for a period of 3
months after last dose of CVM-1118

Exclusion Criteria:

1. Major surgery (other than diagnostic surgery) or radiation therapy within 28 days of
starting study treatment

2. Systemic anticancer therapy (e.g., chemotherapy, hormonal, investigational, biological
therapies) within 28 days (or fewer than 5 half-lives, whichever is shorter) of
starting study treatment except for ongoing hormonal therapy administered for control
of a second cancer (e.g., breast or prostate cancer)

3. Receipt of a CYP3A4 inducer less than 28 days or 5 half-lives of the CYP3A4 inducer
prior to the first day of sorafenib administration

4. Other known active cancer(s) likely to require treatment in the next two (2) years or
likely to impact the assessment of any study endpoints

5. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
therapy (e.g., subjects with known HBV or HCV infections controlled on antivirals are

6. Known Central Nervous system (CNS) metastases unless appropriately treated and
neurologically stable for ≥ 4 weeks off steroids

7. Pregnant or currently breast-feeding

8. Known HIV-positive

9. Patients with impaired gastrointestinal (GI) diseases that may significantly alter the
absorption of oral medications

10. Psychiatric illness/social situations that would interfere with compliance with study

11. History of clinically significant cardiovascular abnormalities such as uncontrolled
hypertension, congestive heart failure (New York Heart Association classification ≥
2), unstable angina, poorly controlled arrhythmias, myocardial infarction within 6
months of study entry

12. Other severe acute or chronic medical or psychiatric conditions or laboratory
abnormalities that would impart, in the judgement of the PI and/or Sponsor, excess
risk associated with study participation or study drug administration, which would
make the subject inappropriate for entry into this study
We found this trial at
Whittier, California 90603
Whittier, CA
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Charleston, South Carolina 29403
Charleston, SC
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Fairfax, Virginia 22031
Fairfax, VA
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138號 Shengli Road
Tainan, 704
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