Anlotinib Combined With Docetaxel for Advanced Non-squamous Non-Small Cell Lung Cancer (ACDFNSNSCLC)
Primary Purpose
Non Small Cell Lung Cancer
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Anlotinib Hydrochloride plus Docetaxel
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring NSCLC Anlotinib Docetaxel
Eligibility Criteria
Inclusion Criteria:
- Signed the informed consent form prior to patient entry;
- EGFR、ALK mutation-negative;Patients who has failed from the first-line Platinum-based Doublet or single chemotherapy with the advanced non-small cell lung cancer and has not used docetaxel;
- ≥ 18 and ≤ 75 years of age;ECOG PS:0-1;Expected Survival Time: Over 3 months;
- Diagnosed with Non-squamous advanced NSCLC (phase IIIB/IV) through pathology, with measurable nidus(using RECIST 1.1)or recurrent non-squamous non-small cell lung cancer
- Patients who has failed from the first-line Platinum-based Doublet chemotherapy with the advanced non-small cell lung cancer (For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment) Noted: failed from prior treatment means(1) progress disease confirmed by CT; cannot tolerable from standard treatment, such as hematologic toxicities ≥ level 4; non-hematologic toxicities ≥ level 3;damages of heart/liver/kidney ≥ level 2 in CTC AE 4.0;
- Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter imaged by CT scan or MRI;prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months;
- Toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in CTC AE (4.0),Which accepts the interval of nitrosourea or mitomycin ≥ 6 weeks;Accept other cytotoxic drugs, anti-tumor angiogenesis therapy such as bevacizumab (Avastin), Endo, etc., surgery ≥ 4 weeks;End of radiotherapy (except for local palliative radiotherapy) ≥ 2 weeks;
- The main organs function are normally, the following criteria are met(1)Blood routine examination criteria should be met (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli): HB≥90 g/L; ANC ≥ 1.5×10^9/L; PLT ≥80×10^9/L;(2)Biochemical examinations must meet the following criteria: TBIL<1.5×ULN; ALT and AST < 2.5×ULN, and for patients with liver metastases < 5×ULN; Serum Cr ≤ 1.25×ULN or endogenous creatinine clearance > 60 ml/min (Cockcroft-Gault formula);
- Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device,contraceptive and condom) throughout treatment and for at least 6 months after study is stopped;the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment,and the patients required to be non-lactating;Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped.
Exclusion Criteria:
- Squamous carcinoma(including Adenosquamous carcinoma); Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
- have used Anlotinib、docetaxel before;
- Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor;
Medical history and combined history:
- Significant brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms);
- The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks;
- Other active malignancies that require simultaneous treatment;
- Patients with a history of malignant tumors except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone a curative treatment and have no disease recurrence within 5 years from the start of treatment;
- Patients with previous anti-tumor treatment-related adverse reactions (excluding hair loss) who have not recovered to NCI-CTCAE ≤1;
- Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;Note: Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes;
- Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;
- The effects of surgery or trauma have been eliminated for less than 14 days before enrollment in subjects who have undergone major surgery or have severe trauma;
- Severe acute or chronic infections requiring systemic treatment;
- Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50%;
- There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma;
- Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;
- Long-term unhealed wounds or fractures;
- Decompensated diabetes or other ailments treated with high doses of glucocorticoids;
- Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;
- Events of venous/venous thrombosis occurring within the first 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- Planned for systemic anti-tumor therapy, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (4 weeks prior to enrollment in other anti-cancer drug clinical trials or within 4 weeks prior to grouping or during the study period Or use mitomycin C) within 6 weeks prior to receiving the test drug. Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks before grouping or limited-field radiotherapy to be evaluated for tumor lesions within 2 weeks before grouping;
- Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite optimal medical treatment);
- Have a history of psychotropic substance abuse and are unable to quit or have a mental disorder;
- A known history of HIV testing positive or acquired immunodeficiency syndrome (AIDS);untreated active hepatitis (hepatitis b: HBsAg positive and HBV DNA more than 1 x 103 copy /ml; Hepatitis c: HCV RNA is positive and liver function is abnormal); Combined with hepatitis b and hepatitis c infection;
- Serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anlotinib Hydrochloride plus Docetaxel
Arm Description
Anlotinib(12mg QD PO d1-14, 21 days per cycle) plus Docetaxel (75mg/m2 IV d1) Drug: Anlotinib Hydrochloride plus Docetaxel
Outcomes
Primary Outcome Measures
Progress free survival (PFS)
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Secondary Outcome Measures
Overall Survival (OS)
OS is defined as the time until death due to any cause.
Objective Response Rate (ORR)
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Disease Control Rate (DCR)
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Quality of Life score (QoL)
use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.
Full Information
NCT ID
NCT03750916
First Posted
November 20, 2018
Last Updated
November 22, 2018
Sponsor
Qilu Hospital of Shandong University
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03750916
Brief Title
Anlotinib Combined With Docetaxel for Advanced Non-squamous Non-Small Cell Lung Cancer
Acronym
ACDFNSNSCLC
Official Title
Anlotinib Combined With Docetaxel as Second-line Treatment of Patients With Wild-type Advanced Non-squamous NSCLC
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 30, 2018 (Anticipated)
Primary Completion Date
November 30, 2020 (Anticipated)
Study Completion Date
November 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Qilu Hospital of Shandong University
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development. It can inhibit the angiogenesis related kinase, such as VEGFR, FGFR, PDGFR, and tumor cell proliferation related kinase -c-Kit kinase. In the phase Ⅲ study, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months. Therefore,envisage using anlotinib plus docetaxel treat the advanced Non-squamous non-small cell lung cancer to further improve the patient's PFS or OS.
Detailed Description
This is a multicentre single arm clinical trial conducted in China,the purpose of this study is To Evaluate the Effectiveness and Safety of Anlotinib (12mg QD PO d1-14, 21 days per cycle)Combined with Docetaxel (75mg/m2 IV d1) for advanced Non-squamous non-small cell lung cancer.According to the result of TAX317,the PFS of second line standard chemotherapy was 3 month. Expected the PFS was 5.7. Using PASS11, That calculated the sample size of this study was 41 , according to 10% censoring,the expected sample size is 46.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
NSCLC Anlotinib Docetaxel
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Anlotinib and Docetaxel
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anlotinib Hydrochloride plus Docetaxel
Arm Type
Experimental
Arm Description
Anlotinib(12mg QD PO d1-14, 21 days per cycle) plus Docetaxel (75mg/m2 IV d1) Drug: Anlotinib Hydrochloride plus Docetaxel
Intervention Type
Drug
Intervention Name(s)
Anlotinib Hydrochloride plus Docetaxel
Intervention Description
Anlotinib Hydrochloride (12mg QD PO d1-14, 21 days per cycle) and Docetaxel (75mg/m2 IV d1)
Primary Outcome Measure Information:
Title
Progress free survival (PFS)
Description
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Time Frame
each 42 days up to PD or death(up to 24 months)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS is defined as the time until death due to any cause.
Time Frame
From randomization until death (up to 24 months)
Title
Objective Response Rate (ORR)
Description
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Time Frame
each 42 days up to intolerance the toxicity or PD (up to 24 months)
Title
Disease Control Rate (DCR)
Description
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Time Frame
each 42 days up to intolerance the toxicity or PD (up to 24 months)
Title
Quality of Life score (QoL)
Description
use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.
Time Frame
each 42 days up to intolerance the toxicity or PD (up to 24 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed the informed consent form prior to patient entry;
EGFR、ALK mutation-negative;Patients who has failed from the first-line Platinum-based Doublet or single chemotherapy with the advanced non-small cell lung cancer and has not used docetaxel;
≥ 18 and ≤ 75 years of age;ECOG PS:0-1;Expected Survival Time: Over 3 months;
Diagnosed with Non-squamous advanced NSCLC (phase IIIB/IV) through pathology, with measurable nidus(using RECIST 1.1)or recurrent non-squamous non-small cell lung cancer
Patients who has failed from the first-line Platinum-based Doublet chemotherapy with the advanced non-small cell lung cancer (For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment) Noted: failed from prior treatment means(1) progress disease confirmed by CT; cannot tolerable from standard treatment, such as hematologic toxicities ≥ level 4; non-hematologic toxicities ≥ level 3;damages of heart/liver/kidney ≥ level 2 in CTC AE 4.0;
Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter imaged by CT scan or MRI;prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months;
Toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in CTC AE (4.0),Which accepts the interval of nitrosourea or mitomycin ≥ 6 weeks;Accept other cytotoxic drugs, anti-tumor angiogenesis therapy such as bevacizumab (Avastin), Endo, etc., surgery ≥ 4 weeks;End of radiotherapy (except for local palliative radiotherapy) ≥ 2 weeks;
The main organs function are normally, the following criteria are met(1)Blood routine examination criteria should be met (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli): HB≥90 g/L; ANC ≥ 1.5×10^9/L; PLT ≥80×10^9/L;(2)Biochemical examinations must meet the following criteria: TBIL<1.5×ULN; ALT and AST < 2.5×ULN, and for patients with liver metastases < 5×ULN; Serum Cr ≤ 1.25×ULN or endogenous creatinine clearance > 60 ml/min (Cockcroft-Gault formula);
Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device,contraceptive and condom) throughout treatment and for at least 6 months after study is stopped;the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment,and the patients required to be non-lactating;Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped.
Exclusion Criteria:
Squamous carcinoma(including Adenosquamous carcinoma); Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
have used Anlotinib、docetaxel before;
Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor;
Medical history and combined history:
Significant brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms);
The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks;
Other active malignancies that require simultaneous treatment;
Patients with a history of malignant tumors except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone a curative treatment and have no disease recurrence within 5 years from the start of treatment;
Patients with previous anti-tumor treatment-related adverse reactions (excluding hair loss) who have not recovered to NCI-CTCAE ≤1;
Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;Note: Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes;
Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;
The effects of surgery or trauma have been eliminated for less than 14 days before enrollment in subjects who have undergone major surgery or have severe trauma;
Severe acute or chronic infections requiring systemic treatment;
Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50%;
There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma;
Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;
Long-term unhealed wounds or fractures;
Decompensated diabetes or other ailments treated with high doses of glucocorticoids;
Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;
Events of venous/venous thrombosis occurring within the first 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
Planned for systemic anti-tumor therapy, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (4 weeks prior to enrollment in other anti-cancer drug clinical trials or within 4 weeks prior to grouping or during the study period Or use mitomycin C) within 6 weeks prior to receiving the test drug. Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks before grouping or limited-field radiotherapy to be evaluated for tumor lesions within 2 weeks before grouping;
Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite optimal medical treatment);
Have a history of psychotropic substance abuse and are unable to quit or have a mental disorder;
A known history of HIV testing positive or acquired immunodeficiency syndrome (AIDS);untreated active hepatitis (hepatitis b: HBsAg positive and HBV DNA more than 1 x 103 copy /ml; Hepatitis c: HCV RNA is positive and liver function is abnormal); Combined with hepatitis b and hepatitis c infection;
Serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wang Xiuwen, doctor
Phone
008618560082906
Email
wangxiuwen@medmail.com.cn
12. IPD Sharing Statement
Learn more about this trial
Anlotinib Combined With Docetaxel for Advanced Non-squamous Non-Small Cell Lung Cancer
We'll reach out to this number within 24 hrs