Treatment of Advanced Intrahepatic Cholangiocarcinoma (TAICC)
Primary Purpose
ICC
Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Levamisole Hydrochloride
Anlotinib Hydrochloride Capsules
Sponsored by
About this trial
This is an interventional treatment trial for ICC
Eligibility Criteria
Inclusion Criteria:
- 1. Ages 18-65 years
- 2. The diagnosis of ICC: in accordance with "diagnostic and treating standards on primary liver cancer" or histological/cytological diagnosis of primary liver cancer
- 3. Un-resectable HCC : patients with developing primary liver cancer of Barcelona stage(BCLC) B; multiple nodules (less than 5, the total diameter of less than 20 cm), no invasion, no symptoms;refusing open surgical treatment and volunteering for the treatment
- 4. The First-line system therapy failure (or residual lesion) from the group of this study a signed informed consent (time) for 2 weeks or more basic returned to normal and adverse events (NCI CTCAE Ⅰ level or less);
- 5. Child-Pugh liver function class A/B(score: ≤7)
- 6. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale in one week before admission
- 7. Estimated survival time > 3 months
- 8. HBV DNA#2000 IU/ml#10^4 copies/ml); or HBV DNA≥2000 IU/ml and are accepting effective antiviral therapy
9. The major organ function is normal. that is meeting the following standards:
Blood routine examination: (No blood transfusion, no G-CSF and no medication were corrected within 14 days before screening)
a.HB≥80g/L# b.ANC≥1.5×109/L#c.PLT≥50×109/L#
Biochemical examination: (ALB was not transfused within 14 days before screening) a.ALB ≥29 g/L# b.ALT#AST<5ULN#c.TBIL ≤3ULN#d.creatinine
- 1.5ULN( albumin and bilirubin, two indicators of Child-Pugh liver function class, can only have one for 2 points)
- 10. For women of childbearing age, the results of serum/urine pregnancy tests must be negative within 7 days before initiation of treatment. All men and women who participate in the study have to take reliable contraceptive measures within the trial and eight weeks after the trial is completed
- 11. volunteers must signed informed consent
Exclusion Criteria:
- 1. With a history of alimentary tract hemorrhage or a definite tendency of gastrointestinal bleeding, such as varices of fundus of stomach and esophagus with bleeding risk; local active ulcer lesions; fecal occult blood ≥#++#
- 2. Patients with hepatobiliary cell carcinoma, mixed cell carcinoma or lamellar cell carcinoma; in the past (within 5 years) or at the same time suffering from other untreated malignant tumors; excluding cured basal cell carcinoma and carcinoma in situs of cervix
- 3. Patients who are undergoing liver transplantation or have a history of organ transplantation(excluding the patient who has undergone liver transplantation before)
- 4. Patients with an allergic history of Levamisole Hydrochloride and Anlotinib Hydrochloride Capsules
- 5. The blood pressure can not be reduced to the normal range by the antihypertensive drug treatment in patients with hypertension(systolic pressure#140 mmHg, diastolic pressure#90 mmHg)
- 6. Patients with myocardial ischemia or myocardial infarction over grade II or a poorly controlled arrhythmia (including QTc interval: men ≥ 450 ms; women ≥ 470 ms)
- 7. Cardiac functional insufficiency of grade III to IV according to NYHA standard; echocardiography: LVEF#50%
- 8. Many factors that influence oral medication, such as unable to swallow; chronic diarrhea; intestinal obstruction; the situations which significantly affect the use and absorption of drugs
- 9. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 28 days before participating the study
- 10. Dysfunction of blood coagulation(INR#2.0 or PT# 16s#APTT > 43s#TT > 21s#Fbg < 2g/L), having a tendency to bleed or undergoing thrombolysis or anticoagulant therapy; ascites with clinical symptoms, that is requiring therapeutic abdominal paracentesis or drainage or Child-Pugh score ≥2
- 11. Objective evidence of pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug associated pneumonia, and severe lung function impairment in the past and at present
- 12. Urine routine showed that urine protein ≥++ or the urine protein in 24 hours#1.0 g
- 13. Patients who have been treated with potent CYP3A4 inhibitors (ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, telithromycin, troleandomycin, erythromycin, cimetidine and so on) within 28 days before participating the study, or potent CYP3A4 inducers (dexamethasone, phenytoin, rifampin, rifabutin, carbamazepine, phenobarbitone and so on) within 12 days before participating the study.
- 14. Pregnant or lactating women; fertile patients who are unwilling or unable to adopt effective contraceptives
- 15. Patients with mental sickness or the history of psychotropic drug abuse
- 16. Patients with severe infection (unable to control the infection effectively)
- 17. The treatment history affecting this program or its efficacy, such as stem cell transplantation, immune regulation (including PD-1 and other test regimens) recently (within half a year)
- 18. The researchers believe that any other factors unsuitable for entering into the study.
Sites / Locations
- The First Affiliated Hospital of Zhengzhou UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
One-drug Regimes
Two-Drug Regimens
Arm Description
Basic drug : Anlotinib Hydrochloride Capsules
Basic drug: Anlotinib Hydrochloride Capsules Add Intervention drug: Levamisole Hydrochloride
Outcomes
Primary Outcome Measures
Progression-free Survival
Time from start of treatment until the first documented event of symptomatic progression or death.
Secondary Outcome Measures
Overall Survival
Time from start of treatment to death from any cause, or last known date of survival
Full Information
NCT ID
NCT03940378
First Posted
April 9, 2019
Last Updated
May 4, 2019
Sponsor
The First Affiliated Hospital of Zhengzhou University
Collaborators
First Affiliated Hospital of Xinjiang Medical University, Luoyang Central Hospital, Nanyang Central Hospital, Anyang Tumor Hospital, Third People's Hospital of Jiaozuo, Sanmenxia Central Hospital, pinmei Group General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03940378
Brief Title
Treatment of Advanced Intrahepatic Cholangiocarcinoma
Acronym
TAICC
Official Title
The Efficacy of Levamisole Hcl in Advanced Intrahepatic Cholangiocarcinoma . A Multicenter, Open, Randomized, Prospective Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
February 1, 2023 (Anticipated)
Study Completion Date
February 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Zhengzhou University
Collaborators
First Affiliated Hospital of Xinjiang Medical University, Luoyang Central Hospital, Nanyang Central Hospital, Anyang Tumor Hospital, Third People's Hospital of Jiaozuo, Sanmenxia Central Hospital, pinmei Group General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Levamisole Hcl in the treatment of patients with advanced intrahepatic cholangiocarcinoma.
Detailed Description
Intrahepatic cholangiocarcinoma(ICC) ,a kind of Hepatocellular carcinoma, is the sixth most common cancer and thesecond leading cause of cancer-related deaths in the world.Currently, Surgical resection is still the main treatment methods of early the ICC, but that is high recurrent . Levamisole Hcl is a broad spectrum of intestinal worm medicine, our previous study have found levamisole could significantly promote the apoptosis of bile duct cancer cells, restrain the progress of the bile duct carcinoma in clinic and prolong survival time.This drug is applicable to a variety of reasons caused by intrahepatic bile duct carcinoma and extrahepatic bile duct carcinoma,so we carry out the study to evaluate the efficacy and safety of Levamisole Hcl in the treatment of patients with advanced intrahepatic cholangiocarcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ICC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
152 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
One-drug Regimes
Arm Type
Experimental
Arm Description
Basic drug : Anlotinib Hydrochloride Capsules
Arm Title
Two-Drug Regimens
Arm Type
Experimental
Arm Description
Basic drug: Anlotinib Hydrochloride Capsules Add Intervention drug: Levamisole Hydrochloride
Intervention Type
Drug
Intervention Name(s)
Levamisole Hydrochloride
Other Intervention Name(s)
LH
Intervention Description
Levamisole Hydrochloride Levamisole Hydrochloride 25mg/tablet; 150mg/d; po;
Intervention Type
Drug
Intervention Name(s)
Anlotinib Hydrochloride Capsules
Other Intervention Name(s)
AHC
Intervention Description
Anlotinib Hydrochloride Capsules Anlotinib Hydrochloride Capsules 12mg / capsule; 12mg/d; po;
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
Time from start of treatment until the first documented event of symptomatic progression or death.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Time from start of treatment to death from any cause, or last known date of survival
Time Frame
48 months
Other Pre-specified Outcome Measures:
Title
Disease Control Rate (DCR)
Description
the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease
Time Frame
28 days
Title
Objective Response Rate(ORR)
Description
Proportion of patients with reduction in tumor burden of a predefined amount
Time Frame
28 days
Title
The change of AFP biomarker
Description
Concentration of AFP biomarker change in tumor markers
Time Frame
approximately 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Ages 18-65 years
2. The diagnosis of ICC: in accordance with "diagnostic and treating standards on primary liver cancer" or histological/cytological diagnosis of primary liver cancer
3. Un-resectable HCC : patients with developing primary liver cancer of Barcelona stage(BCLC) B; multiple nodules (less than 5, the total diameter of less than 20 cm), no invasion, no symptoms;refusing open surgical treatment and volunteering for the treatment
4. The First-line system therapy failure (or residual lesion) from the group of this study a signed informed consent (time) for 2 weeks or more basic returned to normal and adverse events (NCI CTCAE Ⅰ level or less);
5. Child-Pugh liver function class A/B(score: ≤7)
6. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale in one week before admission
7. Estimated survival time > 3 months
8. HBV DNA#2000 IU/ml#10^4 copies/ml); or HBV DNA≥2000 IU/ml and are accepting effective antiviral therapy
9. The major organ function is normal. that is meeting the following standards:
Blood routine examination: (No blood transfusion, no G-CSF and no medication were corrected within 14 days before screening)
a.HB≥80g/L# b.ANC≥1.5×109/L#c.PLT≥50×109/L#
Biochemical examination: (ALB was not transfused within 14 days before screening) a.ALB ≥29 g/L# b.ALT#AST<5ULN#c.TBIL ≤3ULN#d.creatinine
1.5ULN( albumin and bilirubin, two indicators of Child-Pugh liver function class, can only have one for 2 points)
10. For women of childbearing age, the results of serum/urine pregnancy tests must be negative within 7 days before initiation of treatment. All men and women who participate in the study have to take reliable contraceptive measures within the trial and eight weeks after the trial is completed
11. volunteers must signed informed consent
Exclusion Criteria:
1. With a history of alimentary tract hemorrhage or a definite tendency of gastrointestinal bleeding, such as varices of fundus of stomach and esophagus with bleeding risk; local active ulcer lesions; fecal occult blood ≥#++#
2. Patients with hepatobiliary cell carcinoma, mixed cell carcinoma or lamellar cell carcinoma; in the past (within 5 years) or at the same time suffering from other untreated malignant tumors; excluding cured basal cell carcinoma and carcinoma in situs of cervix
3. Patients who are undergoing liver transplantation or have a history of organ transplantation(excluding the patient who has undergone liver transplantation before)
4. Patients with an allergic history of Levamisole Hydrochloride and Anlotinib Hydrochloride Capsules
5. The blood pressure can not be reduced to the normal range by the antihypertensive drug treatment in patients with hypertension(systolic pressure#140 mmHg, diastolic pressure#90 mmHg)
6. Patients with myocardial ischemia or myocardial infarction over grade II or a poorly controlled arrhythmia (including QTc interval: men ≥ 450 ms; women ≥ 470 ms)
7. Cardiac functional insufficiency of grade III to IV according to NYHA standard; echocardiography: LVEF#50%
8. Many factors that influence oral medication, such as unable to swallow; chronic diarrhea; intestinal obstruction; the situations which significantly affect the use and absorption of drugs
9. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 28 days before participating the study
10. Dysfunction of blood coagulation(INR#2.0 or PT# 16s#APTT > 43s#TT > 21s#Fbg < 2g/L), having a tendency to bleed or undergoing thrombolysis or anticoagulant therapy; ascites with clinical symptoms, that is requiring therapeutic abdominal paracentesis or drainage or Child-Pugh score ≥2
11. Objective evidence of pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug associated pneumonia, and severe lung function impairment in the past and at present
12. Urine routine showed that urine protein ≥++ or the urine protein in 24 hours#1.0 g
13. Patients who have been treated with potent CYP3A4 inhibitors (ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, telithromycin, troleandomycin, erythromycin, cimetidine and so on) within 28 days before participating the study, or potent CYP3A4 inducers (dexamethasone, phenytoin, rifampin, rifabutin, carbamazepine, phenobarbitone and so on) within 12 days before participating the study.
14. Pregnant or lactating women; fertile patients who are unwilling or unable to adopt effective contraceptives
15. Patients with mental sickness or the history of psychotropic drug abuse
16. Patients with severe infection (unable to control the infection effectively)
17. The treatment history affecting this program or its efficacy, such as stem cell transplantation, immune regulation (including PD-1 and other test regimens) recently (within half a year)
18. The researchers believe that any other factors unsuitable for entering into the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zujiang Yu, pro
Phone
0086-0371-67966942
Email
johnyuem@zzu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zujiang Yu
Organizational Affiliation
The First Affiliated Hospital of Zhengzhou University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zujiang Yu, pro
Phone
0086-0371-67966942
Email
johnyuem@zzu.edu.cn
First Name & Middle Initial & Last Name & Degree
Juan Li, pro
Phone
0086-0371-67966942
Email
ananli1984@126.com
12. IPD Sharing Statement
Learn more about this trial
Treatment of Advanced Intrahepatic Cholangiocarcinoma
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