Advanced Hepatocellular CarcinomaPhase 2NCT04052152
Anlotinib Hydrochloride Combined With Sintilimab Injection in the Treatment of Advanced Hepatocellular Carcinoma (HCC)
A Phase 2 study testing Anlotinib and Sintilimab injection in people with Advanced Hepatocellular Carcinoma, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This is a single-arm, open-label and exploratory clinical study of Anlotinib Hydrochloride Capsules combined with Sintilimab injection in the treatment of advanced Hepatocellular Carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- Anlotinib and Sintilimab injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 10 Jun 2019to 30 Dec 2021
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least one measurable lesion (the length of spiral CT scan (> 10mm) meets the requirements of RESCIST 1.1) is found in patients with HCC confirmed by histopathology or cytology or who meet the clinical diagnostic criteria.
- Inability or unwillingness to undergo surgery and transcatheter hepatic artery interventional therapy; if interventional therapy, radiotherapy or surgery has been accepted, it must be more than 4 weeks, and adverse reactions or wounds have fully recovered.
- No treatment with sorafenib or other systemic treatment was received. Patients who have used interventional chemotherapeutic drugs during interventional therapy may be enrolled in the group.
- Child-Pugh liver function rating: grade A or B; BCLC stage B or C.
- ECOG 0-1
- The life expectancy is more than 12 weeks.
- The main organs are functioning normally.
- Subjects volunteered to join the study, signed informed consent, good compliance, with follow-up.
Who cannot join
- Hepatobiliary and mixed cell carcinomas and fiberboard cell carcinomas are known; other malignant tumors (except cured cutaneous basal cell carcinomas and cervical carcinoma in situ) have been reported in the past or at the same time.
- Pregnant or lactating women.
- Patients with hypertension who could not be well controlled by antihypertensive drugs (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg), patients with myocardial ischemia or myocardial infarction above grade II, arrhythmias with poor control (including QTC interval > 450 ms) and cardiac insufficiency of grade III-IV according to NYHA standard.
- Inability to swallow, chronic diarrhea and intestinal obstruction significantly affect drug use and absorption.
- There are clear concerns about gastrointestinal bleeding (such as local active ulcer lesions, fecal occult blood ++) or more), and there is a history of gastrointestinal bleeding within 6 months.
- Coagulation dysfunction (PT > 16 s, APTT > 43 s, TT > 21 s, Fbg < 2 g/L), with bleeding tendency or undergoing thrombolysis or anticoagulation therapy.
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- Have a history of mental illness or psychotropic drug abuse.
- Peritoneal effusion with clinical symptoms requires therapeutic abdominal puncture or drainage. Or patients with hepatic encephalopathy as well as with liver transplantation.
- Patients with cancer thrombus involving the main portal vein or inferior vena cava.
- Patients with Infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other disease requiring corticosteroids.
- A history of chronic autoimmune diseases, such as systemic lupus erythematosus.
- Patients with a history of inflammatory bowel diseases such as ulcerative enteritis and crohn's disease. Or patients with a history of inflammatory chronic diarrheal diseases such as irritable bowel syndrome.
- Patients with a history of sarcoidosis or tuberculosis.
- Patients with active hepatitis b, c and HIV infection; HBVER who could controll HBV DNA<500 copy/ml after antiviral treatment is allowed to be included.
- Patients who are allergic to components of Sintilimab injection and anlotinib preparations, or have a history of severe allergic reactions to other monoclonal antibodies.
- Having a history of psychotropic substance abuse and being unable to quit or having a mental disorder.
- Patients with a history of immunodeficiency, or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and hematopoietic stem cell transplantation.
- First dose immunosuppressive drugs used in the first 4 weeks, not including the nasal spray, inhalation, or other ways of topical corticosteroids or physiological doses of systemic corticosteroids (no more than 10 mg/day prednisone or other equivalent dose glucocorticoids). But temporary use of glucocorticoids is permitted for the treatment of dyspnea symptoms of asthma, chronic obstructive pulmonary disease and other diseases.
- Systemic immunostimulant therapy was administered within 4 weeks prior to first administration or planned during the study period. Or systemic immunostimulant therapy was received within 4 weeks.
- According to the researchers' judgment, there are serious concomitant diseases that endanger patient safety or prevent patients from completing the study.
- Drug combinations that have an effect on the metabolism of CYP3A.
- Urinary protein 2+ or 24-hour urinary protein >1g.
- Central nervous system metastasis has occurred.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029
Yongqian Shu, PhD, 00862568306428, shuyongqian@csco.org.cn
Xiaofeng Chen, PhD, 008613585172066, xiaofengch198019@126.com
About this study
Official title: Anlotinib Hydrochloride Capsules Combined With Sintilimab Injection in the Treatment of Advanced Hepatocellular Carcinoma (HCC) Open, Single Arm, Exploratory Clinical Trial
This is a single-arm, open-label and exploratory clinical study of Anlotinib Hydrochloride Capsules combined with Sintilimab injection in the treatment of advanced Hepatocellular Carcinoma (HCC).
In oder to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with Sintilimab injection. Subjects with pathological confirmed Hepatocellular Carcinoma will be enrolled.
21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again.
Read the detailed description
This is a single-arm, open-label and exploratory clinical study of Anlotinib Hydrochloride Capsules combined with Sintilimab injection in the treatment of advanced Hepatocellular Carcinoma (HCC).In oder to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with Sintilimab injection.subjects with pathological confirmed Hepatocellular Carcinoma will be enrolled.21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- Anlotinib and Sintilimab injection
- Keywords
- HCC, Antiangiogenic agents combined with PD-1 antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anlotinib and Sintilimab injectionDrug
Patients will be treated with Anlotinib and Sintilimab injection
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Patients in the study group will receive the following treatment:
21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again Receives: Drug: Anlotinib and Sintilimab injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
the best Objective Response Rate
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Adverse reaction rate
Observe all the participants in any adverse events occurred during the period of clinical research, including clinical symptoms and signs of life, an abnormal in laboratory tests, record its clinical characteristics, severity, occurrence time, duration, treatment and prognosis, and determine its and the correlation between test drugs. NCI-CTC AE 5.0 standard was used to evaluate drug safety.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Secondary outcomes (4)
Progression Free Survival (PFS)
Progression Free Survival
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Duration of Response (DOR)
Duration of Response
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Disease Control Rate (DCR)
the Rate of Disease Control
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Overall survival (OS)
Overall Survival
Measured: From date of randomization until the date of patient died, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2019
- Study start10 Jun 2019
- Primary completion30 Dec 2019 (estimated)
- Study completion30 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yongqian Shu, PhD, Principal investigator, JANGSU PROVINCE HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04052152
- Sponsor's protocol ID
- KEEP-G 04
- Status last verified
- Jul 2019
- First submitted
- 16 Jul 2019
- Last updated
- 9 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen X, Li W, Wu X, Zhao F, Wang D, Wu H, Gu Y, Li X, Qian X, Hu J, Li C, Xia Y, Rao J, Dai X, Shao Q, Tang J, Li X, Shu Y. Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study. Front Oncol. 2022 May 31;12:909035. doi: 10.3389/fonc.2022.909035. eCollection 2022.
PubMed 35712486
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anlotinib Hydrochloride Capsules Combined With Sintilimab Injection in the Treatment of Advanced Hepatocellular Carcinoma (HCC) Open, Single Arm, Exploratory Clinical Trial
- ClinicalTrials.gov ID
- NCT04052152
- Acronym / sponsor ID
- KEEP-G 04
- Conditions
- Advanced Hepatocellular Carcinoma
- Keywords
- HCC, Antiangiogenic agents combined with PD-1 antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 10 Jun 2019 (actual)
- Primary completion
- 30 Dec 2019 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 9 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, open-label and exploratory clinical study of Anlotinib Hydrochloride Capsules combined with Sintilimab injection in the treatment of advanced Hepatocellular Carcinoma (HCC).
In oder to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with Sintilimab injection. Subjects with pathological confirmed Hepatocellular Carcinoma will be enrolled.
21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again.
Detailed description
This is a single-arm, open-label and exploratory clinical study of Anlotinib Hydrochloride Capsules combined with Sintilimab injection in the treatment of advanced Hepatocellular Carcinoma (HCC).In oder to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with Sintilimab injection.subjects with pathological confirmed Hepatocellular Carcinoma will be enrolled.21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Anlotinib and Sintilimab injectionPatients in the study group will receive the following treatment: 21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- At least one measurable lesion (the length of spiral CT scan (> 10mm) meets the requirements of RESCIST 1.1) is found in patients with HCC confirmed by histopathology or cytology or who meet the clinical diagnostic criteria.
- Inability or unwillingness to undergo surgery and transcatheter hepatic artery interventional therapy; if interventional therapy, radiotherapy or surgery has been accepted, it must be more than 4 weeks, and adverse reactions or wounds have fully recovered.
- No treatment with sorafenib or other systemic treatment was received. Patients who have used interventional chemotherapeutic drugs during interventional therapy may be enrolled in the group.
- Child-Pugh liver function rating: grade A or B; BCLC stage B or C.
- ECOG 0-1
Key exclusion criteria (23 listed)
- Hepatobiliary and mixed cell carcinomas and fiberboard cell carcinomas are known; other malignant tumors (except cured cutaneous basal cell carcinomas and cervical carcinoma in situ) have been reported in the past or at the same time.
- Pregnant or lactating women.
- Patients with hypertension who could not be well controlled by antihypertensive drugs (systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg), patients with myocardial ischemia or myocardial infarction above grade II, arrhythmias with poor control (including QTC interval > 450 ms) and cardiac insufficiency of grade III-IV according to NYHA standard.
- Inability to swallow, chronic diarrhea and intestinal obstruction significantly affect drug use and absorption.
- There are clear concerns about gastrointestinal bleeding (such as local active ulcer lesions, fecal occult blood ++) or more), and there is a history of gastrointestinal bleeding within 6 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anlotinib and Sintilimab injectionPatients will be treated with Anlotinib and Sintilimab injection | Drug | Group A |
Primary outcome
Objective Response Rate (ORR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
the best Objective Response Rate
Adverse reaction rate
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Observe all the participants in any adverse events occurred during the period of clinical research, including clinical symptoms and signs of life, an abnormal in laboratory tests, record its clinical characteristics, severity, occurrence time, duration, treatment and prognosis, and determine its and the correlation between test drugs. NCI-CTC AE 5.0 standard was used to evaluate drug safety.
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Duration of Response (DOR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Disease Control Rate (DCR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Overall survival (OS)
Time frame: From date of randomization until the date of patient died, assessed up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2019.
- Derived from this study: PubMed 35712486Chen X, Li W, Wu X, Zhao F, Wang D, Wu H, Gu Y, Li X, Qian X, Hu J, Li C, Xia Y, Rao J, Dai X, Shao Q, Tang J, Li X, Shu Y. Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study. Front Oncol. 2022 May 31;12:909035. doi: 10.3389/fonc.2022.909035. eCollection 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yongqian Shu, PhD principal investigator
JANGSU PROVINCE HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anlotinib and Sintilimab injection in people with Advanced Hepatocellular Carcinoma, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
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 8 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 9 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yongqian Shu, PhD (00862568306428, shuyongqian@csco.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months). The study lists 2 primary outcomes in all. 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 NCT04052152, which also lists 1 linked publication.
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 9 Aug 2019.