Study of Anlotinib After Lenvatinib in Patients With Hepatocellular Carcinoma (ALTER-H-002)

April 1, 2020 updated by: Shanghai Zhongshan Hospital

A Single Arm, Open-label Study of Anlotinib in Patients With Hepatocellular Carcinoma (HCC) After Lenvatinib

This clinical study evaluates the efficacy and safety of anlotinib in patients with hepatocellular carcinoma who have progressed on lenvatinib treatment. It is a single arm, open-label clinical trial conducted in China, and plan to recruit 28 patients. Primary endpoint of the study is Progress Free Survival.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferative signaling. The prime targets of anlotinib include receptor tyrosine kinases vascular endothelial growth factor receptor1 to 3 (VEGFR1-3), fibroblast growth factor receptor 1 to 4 (FGFR1-4), platelet-derived growth factor receptor α and β (PDGFR α, β), and stem cell factor receptor.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
      • Shanghai, China, 200032
        • Recruiting
        • 180 Fenglin Road

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients participate in the study voluntarily and sign informed consent.
  • Histological or cytological confirmation of hepatocellular carcinoma (HCC) or non-invasive diagnosis of HCC as per Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition).
  • Barcelona Clinic Liver Cancer stage Category C or B that cannot benefit from local treatment.
  • Liver function status Child-Pugh Class A or Class B (≤7 points).
  • Failure to prior treatment with lenvatinib according to the RECIST1.1. The last dose of lenvatinib should be over 2 weeks and within 10 weeks before the first dose of anlotinib.
  • At least one measurable lesion according to the RECIST1.1.
  • Eastern Cooperative Oncology Group Performance Status 0 or 1. Life expectancy of at least 3 months.
  • Main organs function is normal. (normal main organs function as defined below: Hemoglobin (Hb) ≥ 90 g/L, Neutrophils (ANC) ≥ 1.5×109/L, Platelet count (PLT) ≥ 60×109/L, Albumin≥ 28g/L, Total bilirubin (TBIL) ≤ 2.0 × normal upper limit (ULN), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3.0 ×ULN, Serum creatinine (Cr) ≤ 1.5× ULN, Hepatitis B virus DNA (HBV-DNA)<1000copy/ml.)
  • The woman patients of childbearing age who must agree to take contraceptive methods (e.g. intrauterine device, contraceptive pill or condom) during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; The man patients who must agree to take contraceptive methods during the research and within another 6 months after it.

Exclusion Criteria:

  • Diagnosed with cholangiocellular carcinoma, mixed cell carcinoma and fibrolamellar hepatocellular carcinoma.
  • History of other malignancy within 5 years or for now (except for non-melanoma skin cancer, cervix in situ carcinoma, superficial Bladder neoplasms).
  • Liver function status Child-Pugh Class C, with malignant ascites.
  • Any major unhealed wound, ulcer, or fracture occurred in a patient who had undergone major surgery or trauma within 4 weeks and/or had any bleeding or bleeding episodes which the degree is bigger than Common Terminology Criteria for Adverse Events (CTCAE) 3 grade within 4 weeks prior to enrollment.
  • Participated in other anti-tumor clinical trials within 4 weeks.
  • Prior systemic treatment for HCC, except lenvatinib. Intolerance of lenvatinib (defined as not less than 20 days at a minimum daily dose of 400 mg within the last 28 days).
  • Symptoms that affect oral medication and cannot be controlled through proper treatment (such as inability to swallow, chronic diarrhoea and intestinal obstruction, etc.).
  • Known history or symptomatic metastatic brain or meningeal tumors.
  • Patients with arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism.
  • History of gastrointestinal bleeding due to severe gastroesophageal varices or definite tendency of gastrointestinal bleeding, or definite gastrointestinal bleeding tendency due to other causes, such as active ulcer, ulcerative colitis, etc. Fecal occult blood ≥ ++.
  • Any of the following coagulation functions are abnormal, including: Prothrombin time (PT)>16 s, Activated partial thromboplastin time (APTT) >48 s, Thrombin time (TT)>21 s, International normalized ratio (INR)>2, fibrinogen (FIB)<2 g/L.
  • Patients who underwent major surgery within 4 weeks.
  • Patients who have got non remissive toxic reactions derived from lenvatinib treatment, which is over level 2 in CTC AE (4.0).
  • Patients with any severe and/or unable to control diseases，including： Patients with unsatisfactory blood pressure control using antihypertensive drugs (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100) mmHg); Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QTc≥480ms) and patients with Grade 2 or higher congestive heart failure (NYHA Classification); Patients with active or unable to control serious infections, which is over level 2 in CTC AE (4.0); Patients with poorly controlled diabetes (fasting blood glucose(FBG)>10mmol/L); Patients with kidney failure who require hemodialysis or peritoneal dialysis; Patients with a history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation; Urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein quantitation > 1.0 g.
  • Patients whose tumors had invaded important blood vessels by imaging or who, as determined by the researchers, were likely to invade important blood vessels during follow-up trial, resulting in fatal bleeding.
  • Female patients who are pregnant or breastfeeding.
  • Patients with drug abuse history and unable to get rid of or patients with mental disorders.
  • Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Anlotinib
Anlotinib p.o., qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent.
Drug: Anlotinib
12mg orally (p.o.) every day (qd) for 2 weeks of every 3 week cycle (i.e. 2 weeks on, 1 week off)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progress free survival (PFS)
Time Frame: each 42 days up to progressive disease (PD) or death (up to 24 months)
Progress free survival is defined as the time from first day of anlotinib treatment until the first date of either objective disease progression or death due to any cause, whichever occurs first.
each 42 days up to progressive disease (PD) or death (up to 24 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From first day of anlotinib treatment until death (up to 24 months)
Overall survival is defined as the time from first day of anlotinib treatment until the date of death due to any cause or the date of the last contact, at which the patients will be censored.
From first day of anlotinib treatment until death (up to 24 months)
Objective Response Rate (ORR)
Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Objective response rate is defined as the percentage of subjects whose best response was complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST1.1).
each 42 days up to intolerance the toxicity or PD (up to 24 months)
Disease Control Rate (DCR)
Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Disease control rate is defined as the percentage of subjects whose best response was CR, PR or stable disease (SD) according to the RECIST1.1.
each 42 days up to intolerance the toxicity or PD (up to 24 months)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: Until 30 day safety follow-up visit
Until 30 day safety follow-up visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanghai Zhongshan Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xiaowu Huang, doctor, Shanghai Zhongshan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 24, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B2019-173R

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings