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Hepatocellular CarcinomaPhase 2NCT03582618

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

A Phase 2 study testing Sorafenib and CVM-1118 in people with Hepatocellular Carcinoma and Advanced Cancer, run by TaiRx, Inc. at 3 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma, Advanced Cancer
What is being tested?
Sorafenib and CVM-1118
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
3 sitesin 2 countries
Study dates
12 Jul 2018to 30 Dec 2022
Phase
Phase 2
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

  • 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:
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  • 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
  • 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)
  • Willingness to participate in collection of pharmacokinetic and other exploratory blood collection as defined in the protocol
  • Willingness to use adequate contraception throughout study and for a period of 3 months after last dose of CVM-1118

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Taiwan2 sites

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, 11502

Other trials in Taiwan

United States1 site

  • Charleston Hematology Oncology Associates

    Charleston, South Carolina, 29403

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Being tested
Sorafenib, CVM-1118
Keywords
Oncology, Hepatocellular Carcinoma (HCC), Sorafenib, Hepatoma
Medical subject headings
Carcinoma, Hepatocellular, Neoplasms

What participants receive

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

  • SorafenibDrug

    Also called Nexavar

    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

  • CVM-1118Drug

    Also called TRX-818

    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

Study groups in NCT03582618
Study groupRoleWhat they receive
Sorafenib + CVM-1118ExperimentalCycle 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.
Receives: Drug: Sorafenib; Drug: CVM-1118

What is being measured

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

  1. Objective Response Rate (ORR)

    Assessment by modified RECIST criteria

    Measured: 24 weeks after the last subject starts CVM-1118

Secondary outcomes (15)

  1. Overall survival (OS)

    Overall survival (OS) is defined as time from first dose of study drug to death

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

  2. Progression-free survival (PFS)

    Progression-free survival (PFS) is defined as time from the first dose of study drug to the time of progression or death

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

  3. Time to progression (TTP)

    Time to progression (TTP) is defined as the time from the first dose of study drug to the time of progression

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

  4. Duration of response (DoR)

    Duration of response (DoR) is defined as time from the first documentation of response to the time of progression

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

  5. Disease control rate (DCR)

    Disease control rate (DCR) is defined as the sum of complete response (CR), partial response (PR), and stable disease rate (SD) as assessed by modified RECIST criteria

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

  6. Rate of Adverse event (AE) and Serious Adverse Event (SAE)

    Rate of Adverse event (AE) and Serious Adverse Event (SAE) are assessed using Common Terminology Criteria for Adverse Events v5 (CTCAE) criteria

    Measured: During the course of trial and within 28 days following the last dose of CVM-1118 or prior to the start of new treatment, whichever comes first

  7. Assessed the baseline and out-of-range vital signs_ body temperature, blood pressure, heart rate, and respiratory rate by CTCAE v4.03

    A list of all laboratory normal ranges will also be provided. Values with CTCAE v4.03 Grade ≧ 3 will be identified with flags.

    Measured: During the course of trial and within 28 days following the last dose of CVM-1118 or prior to the start of new treatment, whichever comes first

  8. Assessed the baseline and out-of range laboratory parameters_hematology, chemistry, coagulation, and urinalysis by CTCAE v4.03

    A list of all laboratory normal ranges will also be provided. Values with CTCAE v4.03 Grade ≧ 3 will be identified with flags.

    Measured: During the course of trial and within 28 days following the last dose of CVM-1118 or prior to the start of new treatment, whichever comes first

  9. Abnormalities in electrocardiography (ECG)

    a 12-lead (with a 10-second rhythm strip) tracing, with a capacity to calculate the standard intervals automatically, will be used.

    Measured: During the course of trial and within 28 days following the last dose of CVM-1118 or prior to the start of new treatment, whichever comes first

  10. Maximum Plasma Concentration [Cmax] of sorafenib, CVM-1118, and its metabolite CVM-1125 after CVM-1118 dosing

    Maximum Plasma Concentration [Cmax] of sorafenib, CVM-1118, and its metabolite CVM-1125 will be measured to see maximum exposure after CVM-1118 dosing

    Measured: During Cycle 1 and Cycle 2 (each cycle is 28 days)

  11. Area Under the Curve [AUC] of sorafenib, CVM-1118, and its metabolite CVM-1125 after CVM-1118 dosing

    Area Under the Curve [AUC] of sorafenib, CVM-1118, and its metabolite CVM-1125 will be measured to see drug exposure after CVM-1118 dosing

    Measured: During Cycle 1 and Cycle 2 (each cycle is 28 days)

  12. Pharmacodynamics analysis for the relationship of Cmax and ORR

    Relationship between Cmax and ORR will be evaluated

    Measured: During Cycle 1 and Cycle 2 (each cycle is 28 days)

  13. Pharmacodynamics analysis for the relationship of AUC and ORR

    Relationship between AUC and ORR will be evaluated

    Measured: During Cycle 1 and Cycle 2 (each cycle is 28 days)

  14. Pharmacodynamics analysis for the relationship of Cmax and Adverse Event (AE)

    Relationship between Cmax and AE will be evaluated

    Measured: During Cycle 1 and Cycle 2 (each cycle is 28 days)

  15. Pharmacodynamics analysis for the relationship of AUC and Adverse Event (AE)

    Relationship between AUC and AE will be evaluated

    Measured: During Cycle 1 and Cycle 2 (each cycle is 28 days)

Timeline

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

  1. First posted11 Jul 2018
  2. Study start12 Jul 2018
  3. Primary completion16 Nov 2021
  4. Study completion30 Dec 2022

Why it stopped: The study has been terminated due to slow enrollment

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03582618
Sponsor's protocol ID
CVM-004
Status last verified
Jan 2023
First submitted
21 May 2018
Last updated
10 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sorafenib and CVM-1118 in people with Hepatocellular Carcinoma and Advanced Cancer, run by TaiRx, Inc. at 3 sites in 2 countries.

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 18 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: stopped early, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Taiwan, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early (reason given: The study has been terminated due to slow enrollment). Results are not available in the source record.

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?

Objective Response Rate (ORR) (time frame: 24 weeks after the last subject starts CVM-1118). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03582618.

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 10 Jan 2023.

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