Anlotinib Combined With Docetaxel Versus Docetaxel for Previous Treated Advanced NSCLC

NCT03726736 | Unknown Phase 1 DMC

• 1 other identifier: ALTER-L016
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  Progress free survival

  each 42 days up to PD or death(up to 24 months)

Secondary Outcomes (5)

• OS

  From randomization until death (up to 24 months)

• quality of life

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• ORR

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• DCR

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Until 21 day safety follow-up visit

Study Arms (2)

Anlotinib combined Docetaxel

EXPERIMENTAL

patients treated with anlotinib and Docetaxel (21 days for 1 cycle) until PD (progressive disease)

Drug: Anlotinib combined Docetaxel

Docetaxel

ACTIVE COMPARATOR

patients treated with Docetaxel (21 days for 1 cycle) until PD (progressive disease)

Drug: Docetaxel

Interventions

Anlotinib combined Docetaxel DRUG

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)

Anlotinib combined Docetaxel

Docetaxel DRUG

Docetaxel (60mg/m2 IV, d1, 21 days per cycle)

Docetaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subjects voluntarily joined the study and signed informed consent, with good compliance and follow-up;
• \. 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);
• \. 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
• \. first line chemotherapy used platinum-based doublet chemotherapy and failed.
• \. 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;
• \. 18\~75 years old, ECOG PS 0-1 points. Life expectancy is at least 3 months.
• \. 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;
• \. The main organs function are normally, the following criteria are met:
• 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;
• 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).
• \. Avoid pregnancy during treatment and 6 month after treatment.

You may not qualify if:

• \. Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
• \. Have used anlotinib / docetaxel before, or have used other VEGFR-TKI drugs.
• \. 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;
• \. History and comorbidities
• 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);
• 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;
• Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite optimal medical treatment);
• 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;

Sponsors & Collaborators

• Yong Fang: lead
• Zhejiang Provincial People's Hospital: collaborator
• Zhejiang Cancer Hospital: collaborator
• Ningbo No. 1 Hospital: collaborator
• Ningbo No.2 Hospital: collaborator
• Affiliated Hospital of Jiaxing University: collaborator
• Huzhou Central Hospital: collaborator

Study Sites (1)

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, 310000, China

RECRUITING

Related Publications (2)

• Shou J, Chen J, Guo Q, Hong W, Wang Y, Rao C, Lu L, Yang X, Zhu D, Lan F, Fang Y, Pan H. Anlotinib in combination with docetaxel for advanced nonsmall cell lung cancer after failure of platinum-based treatment: A phase 1/2 trial. Cancer. 2025 May 15;131(10):e35822. doi: 10.1002/cncr.35822.

  PMID: 40366884 DERIVED

• Pu X, Shou J, Xiao Z, Chen J, Xiao M, Guo Q, Ma Z, Hong W, Wang Q, Wang Y, Li J, Rao C, Weng J, Lu L, Wu L, Fang Y. Anlotinib Plus Docetaxel is Promising in Advanced NSCLC Progressing on First-Line Immunotherapy: A Pooled Analysis of Two Randomized Trials. Adv Ther. 2025 Jul;42(7):3249-3264. doi: 10.1007/s12325-025-03170-2. Epub 2025 May 12.

  PMID: 40354010 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 31, 2018
• Study Start: December 21, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2020
• Last Updated: June 7, 2019

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)