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出境医 / 临床实验 / Clinical Study on the Second-line and Above Treatment of Advanced Solid Tumor With Anlotinib Combined With Pd-1 Antibody

Clinical Study on the Second-line and Above Treatment of Advanced Solid Tumor With Anlotinib Combined With Pd-1 Antibody

Study Description
Brief Summary:
The main objective was to evaluate the safety and efficacy of anlotinib hydrochloride combined with pd-1 antibody second-line and above in the treatment of advanced solid tumors

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: Anlotinib Drug: pd-1 antibody Phase 2 Phase 3

Detailed Description:
To observe the beneficial population and adverse reactions of anlotinib hydrochloride combined with pd-1 in the treatment of patients with advanced solid tumor, and to explore the safe and effective drug treatment dose in the combined program, so that more patients with advanced tumor with poor prognosis can benefit from the combined program
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Exploratory Clinical Study on the Second-line and Above Treatment of Advanced Solid Tumor With Anlotinib Hydrochloride Combined With Pd-1 Antibody: An Open-Label, Single-center, Single-arm Study
Actual Study Start Date : April 8, 2019
Estimated Primary Completion Date : June 8, 2020
Estimated Study Completion Date : July 8, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Anlotinib&pd-1 antibody
Anlotinib 10mg/d,q.d.,p.o.&pd-1 antibody 200mg/d.q.3w.d.l.v
Drug: Anlotinib
Anlotinib Hydrochloride Capsules
Other Name: Fu ke wei

Drug: pd-1 antibody
Pembrolizumabinjection
Other Name: Keytruda

Outcome Measures
Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: up to 2 year ]
    From date of randomization until the date of first documented progression or date of death from any cause


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: up to 1 year ]
    From date of randomization until the date of death from any cause

  2. Disease Control Rate (DCR) [ Time Frame: up to 1 year ]
    Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.

  3. Overall survival(OS) [ Time Frame: up to 2 year ]
    From date of randomization until the date of death from any cause


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed the informed consent form prior to patient entry.
  2. There is at least one measurable lesion in the pathologically diagnosed advanced solid tumor, including non-small cell lung cancer, liver cancer, gastric cancer, colorectal cancer, pancreatic cancer, soft tissue sarcoma, malignant melanoma, gallbladder cancer, esophageal cancer, ovarian cancer, endometrial cancer and breast cancer
  3. ≥ 18 and ≤ 70 years of age.
  4. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
  5. Life expectancy of more than 3 months.
  6. Adequate hepatic, renal, heart, and hematologic functions: ANC ≥ 1.5×109/L, PLT ≥ 100×109/L, HB ≥ 90 g/L, TBIL ≤ 1.5×ULN, ALT or AST ≤ 2.5×ULN (or ≤ 5×ULN in patients with liver metastases), Serum Cr ≤ 1.5×ULN, Cr clearance ≥ 60 mL/min;Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).
  7. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 6 months after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 6 months after last dose of study drug.

Exclusion Criteria:

  1. uncontrollable hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, despite optimal medical therapy), grade II The above myocardial ischemia or myocardial infarction, poor control of arrhythmia (including QTc interval male ≥ 450 ms, female ≥ 470 ms).
  2. Patients previously treated with anticancer therapies also have a Toxicity Level> 1 in NCI CTCAE.
  3. A variety of factors that affect oral absorption (such as inability to swallow, nausea, vomiting, chronic diarrhea, intestinal obstruction, etc.).
  4. Patients with gastrointestinal bleeding risk may not be included, including the following: (1) active peptic ulcer lesions and fecal occult blood (++); (2) history of melena and vomiting within 3 months; (3) ) For fecal occult blood (+) must be gastroscopy, clear whether the existence of gastrointestinal organic diseases.
  5. Coagulation dysfunction (INR> 1.5, PT> ULN + 4s or APTT> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment.
  6. Long-term, unhealed wounds or fractures.
  7. Active bleeding, within 30 days after major surgery.
  8. Intracranial metastasis.
  9. Pregnant or lactating women.
  10. Cytotoxic drug treatment, radiotherapy within 3 weeks after treatment; had taken two or more targeted drugs, or into the group before the other three months have been taking other targeted drugs.
  11. Other malignant tumors in the past 3 years.
  12. The investigators believe there is any condition that may harm the subject or result in the subject's inability to meet or perform the research requirements.
  13. Huge metastasis / recurrence (tumor diameter> 5 cm)。
  14. Malignant pleural effusion or ascites, causing NCI CTCAE grading 2 or more people with dyspnea.
  15. Any allergy to apatinib should be excluded.
  16. Severe liver and kidney dysfunction (grade 4) patients should be excluded.
  17. Persons with a history of substance abuse who can not be abdicated or have mental disorders.
  18. According to the judgment of the researcher, there is a concomitant disease that seriously endangers the patient's safety or affects the patient in completing the study.
Contacts and Locations

Contacts
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Contact: Zibing Wang 18937621301 bingziwang@hotmail.com

Locations
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China, Henan
Henan Cancer Hospital Recruiting
Zhengzhou, Henan, China, 450008
Contact: Zibing Wang         
Sponsors and Collaborators
Henan Cancer Hospital
Cttq
Investigators
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Principal Investigator: Zibing Wang Henan Cancer Hospital
Tracking Information
First Submitted Date  ICMJE May 23, 2019
First Posted Date  ICMJE June 5, 2019
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE April 8, 2019
Estimated Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2019)
Progression-free Survival (PFS) [ Time Frame: up to 2 year ]
From date of randomization until the date of first documented progression or date of death from any cause
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2019)
  • Objective Response Rate (ORR) [ Time Frame: up to 1 year ]
    From date of randomization until the date of death from any cause
  • Disease Control Rate (DCR) [ Time Frame: up to 1 year ]
    Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
  • Overall survival(OS) [ Time Frame: up to 2 year ]
    From date of randomization until the date of death from any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Study on the Second-line and Above Treatment of Advanced Solid Tumor With Anlotinib Combined With Pd-1 Antibody
Official Title  ICMJE Exploratory Clinical Study on the Second-line and Above Treatment of Advanced Solid Tumor With Anlotinib Hydrochloride Combined With Pd-1 Antibody: An Open-Label, Single-center, Single-arm Study
Brief Summary The main objective was to evaluate the safety and efficacy of anlotinib hydrochloride combined with pd-1 antibody second-line and above in the treatment of advanced solid tumors
Detailed Description To observe the beneficial population and adverse reactions of anlotinib hydrochloride combined with pd-1 in the treatment of patients with advanced solid tumor, and to explore the safe and effective drug treatment dose in the combined program, so that more patients with advanced tumor with poor prognosis can benefit from the combined program
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumor
Intervention  ICMJE
  • Drug: Anlotinib
    Anlotinib Hydrochloride Capsules
    Other Name: Fu ke wei
  • Drug: pd-1 antibody
    Pembrolizumabinjection
    Other Name: Keytruda
Study Arms  ICMJE Experimental: Anlotinib&pd-1 antibody
Anlotinib 10mg/d,q.d.,p.o.&pd-1 antibody 200mg/d.q.3w.d.l.v
Interventions:
  • Drug: Anlotinib
  • Drug: pd-1 antibody
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 2, 2019)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 8, 2021
Estimated Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed the informed consent form prior to patient entry.
  2. There is at least one measurable lesion in the pathologically diagnosed advanced solid tumor, including non-small cell lung cancer, liver cancer, gastric cancer, colorectal cancer, pancreatic cancer, soft tissue sarcoma, malignant melanoma, gallbladder cancer, esophageal cancer, ovarian cancer, endometrial cancer and breast cancer
  3. ≥ 18 and ≤ 70 years of age.
  4. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
  5. Life expectancy of more than 3 months.
  6. Adequate hepatic, renal, heart, and hematologic functions: ANC ≥ 1.5×109/L, PLT ≥ 100×109/L, HB ≥ 90 g/L, TBIL ≤ 1.5×ULN, ALT or AST ≤ 2.5×ULN (or ≤ 5×ULN in patients with liver metastases), Serum Cr ≤ 1.5×ULN, Cr clearance ≥ 60 mL/min;Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).
  7. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 6 months after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 6 months after last dose of study drug.

Exclusion Criteria:

  1. uncontrollable hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, despite optimal medical therapy), grade II The above myocardial ischemia or myocardial infarction, poor control of arrhythmia (including QTc interval male ≥ 450 ms, female ≥ 470 ms).
  2. Patients previously treated with anticancer therapies also have a Toxicity Level> 1 in NCI CTCAE.
  3. A variety of factors that affect oral absorption (such as inability to swallow, nausea, vomiting, chronic diarrhea, intestinal obstruction, etc.).
  4. Patients with gastrointestinal bleeding risk may not be included, including the following: (1) active peptic ulcer lesions and fecal occult blood (++); (2) history of melena and vomiting within 3 months; (3) ) For fecal occult blood (+) must be gastroscopy, clear whether the existence of gastrointestinal organic diseases.
  5. Coagulation dysfunction (INR> 1.5, PT> ULN + 4s or APTT> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment.
  6. Long-term, unhealed wounds or fractures.
  7. Active bleeding, within 30 days after major surgery.
  8. Intracranial metastasis.
  9. Pregnant or lactating women.
  10. Cytotoxic drug treatment, radiotherapy within 3 weeks after treatment; had taken two or more targeted drugs, or into the group before the other three months have been taking other targeted drugs.
  11. Other malignant tumors in the past 3 years.
  12. The investigators believe there is any condition that may harm the subject or result in the subject's inability to meet or perform the research requirements.
  13. Huge metastasis / recurrence (tumor diameter> 5 cm)。
  14. Malignant pleural effusion or ascites, causing NCI CTCAE grading 2 or more people with dyspnea.
  15. Any allergy to apatinib should be excluded.
  16. Severe liver and kidney dysfunction (grade 4) patients should be excluded.
  17. Persons with a history of substance abuse who can not be abdicated or have mental disorders.
  18. According to the judgment of the researcher, there is a concomitant disease that seriously endangers the patient's safety or affects the patient in completing the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zibing Wang 18937621301 bingziwang@hotmail.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03975036
Other Study ID Numbers  ICMJE 2019093
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Henan Cancer Hospital
Study Sponsor  ICMJE Henan Cancer Hospital
Collaborators  ICMJE Cttq
Investigators  ICMJE
Principal Investigator: Zibing Wang Henan Cancer Hospital
PRS Account Henan Cancer Hospital
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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