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

NCT03582618 | Terminated Phase 2 FDA Drug

• 1 other identifier: CVM-004
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Hepatocellular Carcinoma; Advanced Cancer

Keywords

Oncology; Hepatocellular Carcinoma (HCC); Sorafenib; Hepatoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Assessment by modified RECIST criteria

  24 weeks after the last subject starts CVM-1118

Secondary Outcomes (15)

• Overall survival (OS)

  24 weeks after the last subject starts CVM-1118 and up to 1 year after the last-dose

• Progression-free survival (PFS)

  24 weeks after the last subject starts CVM-1118 and up to 1 year after the last-dose

• Time to progression (TTP)

  24 weeks after the last subject starts CVM-1118 and up to 1 year after the last-dose

• Duration of response (DoR)

  24 weeks after the last subject starts CVM-1118 and up to 1 year after the last-dose

• Disease control rate (DCR)

  24 weeks after the last subject starts CVM-1118 and up to 1 year after the last-dose

Study Arms (1)

Sorafenib + CVM-1118

EXPERIMENTAL

Cycle 0 (at least 3 weeks): sorafenib tolerability assessment period (sorafenib alone) 400mg BID daily (starting dose); The subject will be assessed for the need for a dose reduction in sorafenib during this period. Cycle 1+ (28-day cycles): combination period (sorafenib+CVM-1118) Tolerable dose of sorafenib and CVM-1118 150 (starting dose) or 200 mg BID will be administered continuously for a 28-day cycle until progressive disease, unacceptable toxicity, or consent withdrawal.

Drug: Sorafenib; Drug: CVM-1118

Interventions

Sorafenib DRUG

Sorafenib will be administered orally at a starting dose of 400mg BID daily and the necessity of dose reduction will be assessed during sorafenib tolerability assessment period

Also known as: Nexavar

Sorafenib + CVM-1118

CVM-1118 DRUG

CVM-1118 will be administered orally at 150 mg BID or 200 mg BID daily and combined with the tolerable dose of sorafenib for a 28-day cycle

Also known as: TRX-818

Sorafenib + CVM-1118

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, informed consent
• Age 18 or older (for all treatment locations with exception of Taiwan), or age 20 or older (Taiwan only)
• Pathologically or cytologically-confirmed, advanced-stage hepatocellular carcinoma without prior systemic treatment except for prior immunotherapy and Child-Pugh liver function class A appropriate for treatment with sorafenib
• Measurable disease according to modified Response Evaluation Criteria in Solid Tumors criteria (mRECIST)
• Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1
• Adequate laboratory parameters including:
• 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
• Total serum bilirubin ≤ 2.0 x ULN (except for subjects with documented Gilbert's syndrome who have a limit of ≤ 3.0 x ULN)
• Absolute neutrophil count (ANC):1500/µL
• Platelets: 90,000/µL
• Hemoglobin: 9.0 g/dL
• Serum creatinine ≤ 2.0 x ULN or creatinine clearance of ≥ 50 mL/min
• Serum albumin ≥ 3.0 g/dL
• International normalized ratio (INR) ≤ 1.4
• Prothrombin Time (PT)/ Activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x ULN

You may not qualify if:

• Major surgery (other than diagnostic surgery) or radiation therapy within 28 days of starting study treatment
• Prior systemic immunotherapy for hepatoma within 28 days of starting study treatment
• 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)
• 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
• 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
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy (e.g., subjects with known HBV or HCV infections controlled on antivirals are allowed)
• Known Central Nervous system (CNS) metastases unless appropriately treated and neurologically stable for ≥ 4 weeks off steroids
• Pregnant or currently breast-feeding
• Known HIV-positive
• Patients with impaired gastrointestinal (GI) diseases that may significantly alter the absorption of oral medications
• Psychiatric illness/social situations that would interfere with compliance with study requirements
• 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
• 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

Sponsors & Collaborators

• TaiRx, Inc.: lead

Study Sites (3)

Charleston Hematology Oncology Associates

Charleston, South Carolina, 29403, United States

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 11502, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2018
• First Posted: July 11, 2018
• Study Start: July 12, 2018
• Primary Completion: November 16, 2021
• Study Completion: December 30, 2022
• Last Updated: January 10, 2023

Record last verified: 2023-01

Locations

US (1); TW (2)