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Anlotinib Combined With Docetaxel Versus Docetaxel for Previous Treated Advanced NSCLC (ACWDVDFPTAN)

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ClinicalTrials.gov Identifier: NCT03726736
Recruitment Status : Recruiting
First Posted : October 31, 2018
Last Update Posted : June 7, 2019
Sponsor:
Collaborators:
Zhejiang Provincial People’s Hospital
Zhejiang Cancer Hospital
Ningbo No. 1 Hospital
Ningbo No.2 Hospital
The First Hospital of Jiaxing
Huzhou Central Hospital
Information provided by (Responsible Party):
Yong Fang, Sir Run Run Shaw Hospital

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(12mg,po. qd. on day 1to14 of a 21-day cycle) 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,we envisage using anlotinib plus docetaxel treat the EGFR wild-type advanced Non-small cell lung cancer patients who were failure in the treatment of chemotherapy with platinum containing drugs, to further improve the patient's PFS or OS.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Anlotinib combined Docetaxel Drug: Docetaxel Phase 1 Phase 2

Detailed Description:

This multicentre randomised controlled clinical trial conducted in China include phase I study and phase II study.

Phase I study: to get the maximum tolerated dose of anlotinib when combined with Docetaxel.

Phase II study: to compare the effectiveness and safety of Anlotinib Plus Docetaxel in patients of EGFR wild-type Advanced Non-squamous Non-small Cell Lung Cancer.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Anlotinib Combined With Docetaxel Versus Docetaxel for Platinum-based Therapy Treated Advanced NSCLC: a Multicentre, Randomised Explorative Trial
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : November 1, 2019
Estimated Study Completion Date : November 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: Anlotinib combined Docetaxel
patients treated with anlotinib and Docetaxel (21 days for 1 cycle) until PD (progressive disease)
Drug: Anlotinib combined Docetaxel
Anlotinib ( dose base on phase I study, QD PO d1-14, 21 days per cycle) and Docetaxel (60mg/m2 IV, d1, 21 days per cycle)

Active Comparator: Docetaxel
patients treated with Docetaxel (21 days for 1 cycle) until PD (progressive disease)
Drug: Docetaxel
Docetaxel (60mg/m2 IV, d1, 21 days per cycle)




Primary Outcome Measures :
  1. PFS [ Time Frame: each 42 days up to PD or death(up to 24 months) ]
    Progress free survival


Secondary Outcome Measures :
  1. OS [ Time Frame: From randomization until death (up to 24 months) ]
    Overall Survival

  2. quality of life [ Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months) ]
    use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life

  3. ORR [ Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months) ]
    Objective Response Rate

  4. DCR [ Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months) ]
    Disease Control Rate

  5. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Until 21 day safety follow-up visit ]
    Record Adverse Events (AEs) according to CTCAE (V4.03). To find Potential adverse reaction, measure blood pressure at least 2 times a week and test blood routine, Blood biochemical, Urine routine, stool routine, coagulation function, electrocardiogram for each follow-up, record and analyze the number of abnormal data.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Subjects voluntarily joined the study and signed informed consent, with good compliance and follow-up;
  • 2. Diagnosed as locally advanced and / or metastatic non-small cell lung adenocarcinoma (NSCLC) by cytology or histology; diagnosed as stage IIIB, IIIC or IV according to the 2017 new version of the UICC lung cancer staging criteria (8th edition);
  • 3. At least one target lesion that has not received local treatment in the past 3 months, and accurate measurement by magnetic resonance imaging (MRI) or computed tomography (CT) in at least 1 direction
  • 4. first line chemotherapy used platinum-based doublet chemotherapy and failed.
  • 5. Provide detectable specimens (tissue or cancerous pleural effusion) for genotyping before enrollment, and the patients should be with negative EGFR, ALK, and ROS1 gene test results;
  • 6. 18~75 years old, ECOG PS 0-1 points. Life expectancy is at least 3 months.
  • 7. The damage subjects received from other treatments has recovered(NCI-CTCAE version 4.0 grade ≤ 1), the interval of subjects receiving nitrosourea or mitomycin should be at least 6 weeks; the interval subjects receiving other cytotoxic drugs, bevacate Avastin (Avastin), surgery should be at least 4 weeks; the interval subjects receiving radiotherapy (except for local palliative radiotherapy) should be at least 2 weeks;
  • 8. 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).
  • 9. Avoid pregnancy during treatment and 6 month after treatment.

Exclusion Criteria:

  • 1. Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
  • 2. Have used anlotinib / docetaxel before, or have used other VEGFR-TKI drugs.
  • 3. 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;
  • 4. History and comorbidities

    1. Active 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);
    2. The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks;
    3. Other active malignancies that require simultaneous treatment;
    4. 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
    5. Patients with previous anti-tumor treatment-related adverse reactions (excluding hair loss) who have not recovered to NCI-CTCAE ≤1;
    6. 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;
    7. 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;
    8. Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;
    9. Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite optimal medical treatment);
    10. 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;
    11. Severe acute or chronic infections requiring systemic treatment;
    12. 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%;
    13. There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma;
    14. Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;
    15. Long-term unhealed wounds or fractures;
    16. Severe weight loss (greater than 10%) within 6 weeks prior to randomization;
    17. Decompensated diabetes or other ailments treated with high doses of glucocorticoids;
    18. Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
    19. 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;
    20. 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;
    21. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03726736


Locations
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China, Zhejiang
Sir Run Run Shaw Hospital Recruiting
Hangzhou, Zhejiang, China, 310000
Contact: Hongming Pan, MD    (86)571 86006926    panhm@srrsh.com   
Sub-Investigator: Yong Fang, MD         
Sponsors and Collaborators
Yong Fang
Zhejiang Provincial People’s Hospital
Zhejiang Cancer Hospital
Ningbo No. 1 Hospital
Ningbo No.2 Hospital
The First Hospital of Jiaxing
Huzhou Central Hospital

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Responsible Party: Yong Fang, professor, Sir Run Run Shaw Hospital
ClinicalTrials.gov Identifier: NCT03726736     History of Changes
Other Study ID Numbers: ALTER-L016
First Posted: October 31, 2018    Key Record Dates
Last Update Posted: June 7, 2019
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action