Clinical Trials /

Anlotinib Hydrochloride Combined With EGFR-Tyrosine Kinase Inhibitor (TKI) in Treating Advanced NSCLC Patients With Acquired Resistance to EGFR-TKI

NCT04007835

Description:

The Single-arm, multicenter study evaluate the safety and efficacy of Anlotinib Hydrochloride combined with EGFR TKIs in treating Advanced NSCLC With acquired Resistance to EGFR TKIs

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Anlotinib Hydrochloride Combined With EGFR-Tyrosine Kinase Inhibitor (TKI) in Treating Advanced NSCLC Patients With Acquired Resistance to EGFR-TKI
  • Official Title: Safety and Efficacy of Anlotinib Hydrochloride Combined With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in Treating Advanced Non-small-cell Lung Cancer (NSCLC) Patients With Acquired Resistance to EGFR TKIs

Clinical Trial IDs

  • ORG STUDY ID: CTONG1803
  • NCT ID: NCT04007835

Conditions

  • NSCLC

Interventions

DrugSynonymsArms
Anlotinib HydrochlorideGefitinib Tablets, Erlotinib Hydrochloride Tablets, Icotinib Hydrochloride TabletsAnlotinib Hydrochloride combined with EGFR-TKI

Purpose

The Single-arm, multicenter study evaluate the safety and efficacy of Anlotinib Hydrochloride combined with EGFR TKIs in treating Advanced NSCLC With acquired Resistance to EGFR TKIs

Detailed Description

      EGFR TKI have been approved as first-line treatment in NSCLC patients harboring EGFR
      mutation. However, the acquired resistance of EGFR-TKI occurs almost constantly. Anlotinib is
      a novel oral multitarget tyrosine kinase inhibitor and primary targeted to Vascular
      Endothelial Growth Factor Receptor (VEGFR), fibroblast growth factor receptor (FGFR) ,
      platelet-derived growth factor receptor (PDGFR) and c-Kit. The ALTER-0303 trial showed that
      patients with advanced non-small cell lung cancer (NSCLC) who received anlotinib as
      third-line or further therapy had more survival benefit. The Single-arm, multicenter study
      evaluate the safety and efficacy of Anlotinib Hydrochloride combined with EGFR TKIs in
      treating Advanced NSCLC With acquired Resistance to EGFR TKIs
    

Trial Arms

NameTypeDescriptionInterventions
Anlotinib Hydrochloride combined with EGFR-TKIExperimentalPatients receive anlotinib (12 mg orally daily for 14 days every 21 days cycle) combined with one of following EGFR-TKIs: Gefitinib is administered 250 mg once per day. Erlotinib is administered 150 mg once per day , or Icotinib is administered 125 mg three times per day, until disease progression or untolerated toxicity.
  • Anlotinib Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Patients voluntarily participate in this study, signed and dated informed consent with
             good compliance and follow-up;

          -  Males or females aged 18 Years to 75 Years

          -  The patients should be confirmed with EGFR mutation [e.g., T 790 M , exon 19 deletion,
             L 858 R, etc],

          -  Cytologically or histologically confirmed locally advanced and / or metastatic
             non-small cell lung cancer (NSCLC).

          -  Patients should be using the EGFR TKI monotherapy as the first line treatment and meet
             the following criteria:

               1. Patients who showed objective clinical benefit from treatment with an EGFR

                  TKI as defined by either:

                    -  Patients who showed complete (CR) or partial response (PR) ≥ 4 months, or

                    -  Patients who maintained stable disease (SD) status ≥ 6 months

               2. Patients who showed 1. risk of recurrence and progression, 2. gradual progression
                  or local progression while on continuous treatment with EGFR TKI within the last
                  28 days prior to enrollment.( For recurrent diseases, patients can be accepted
                  with adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy
                  plus adjuvant chemotherapy in the past, and 3. relapse occurs 6 months after the
                  end of treatment).

                    1. CEA≥10ng/ml;

                    2. Gradual progression: Disease control lasting ≥6 months with EGFR-TKI
                       treatment, Compared with the previous assessment, no significant increment
                       of tumor burden and progressive involvement of non-target lesions with a
                       score less than 2, and Symptom scored ≤1. Local progression: Disease control
                       lasting more than 3 months with EGFR-TKI treatment, Progressive disease (PD)
                       due to solitary extracranial lesion or limitation in intracranial lesions
                       (covered by a radiation field),and symptom scored ≤1

                    3. Evidence of imaging or clinical progression is required if progression of
                       disease occurs during the treatment or after the last treatment.

          -  At least one measurable lesion meet the requirements of the standard Response
             Evaluation Criteria In Solid Tumors(RESCIST)version 1.1

          -  Life expectancy is at least 3 months;

          -  Eastern Cooperative Oncology Group(ECOG)Performance Status(PS):0-2.;

          -  The main organs function meet following criteria:

               -  Blood routine examination criteria (no blood transfusion and blood products
                  within 14 days, no correction by Granulocyte Colony-Stimulating Factor (G-CSF)
                  and other hematopoietic stimuli): i) hemoglobin (HB) ≥90g/L ii) Absolute
                  neutrophils count (ANC) ≥1.5×109/L iii) platelet (PLT) ≥80×109/L

               -  Biochemical tests meet the following criteria i) total bilirubin (TBIL) ≤1.5
                  times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and
                  aspartate aminotransferase (AST)≤2.5 ULN, if liver metastasis occurred, ALT and
                  AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.25 ULN or creatinine clearance (CCr)≥45
                  mL/min

          -  Female patients of childbearing age agree that contraceptive measures must be used
             within the study period and within 8 weeks after the end of the study drug treatment.
             The serum or urine test indicates nonpregnant woman within 7 days prior to the study.
             Male patients agree to have contraceptive use during the study period and within 8
             weeks after the end of the study period or have had surgical sterilization.

        Exclusion Criteria:

          -  Small cell lung cancer (including Small cell lung cancer mixed with non-small cell
             lung cancer);

          -  Imaging (CT or MRI) showed that the distance between the lesion and the large vessels
             was less than 5 mm, or there were central tumors invading the local large vessels, or
             there were obvious pulmonary cavity or necrotic tumors.

          -  Patients with active brain metastasis, cancerous meningitis, spinal cord compression,
             or with brain or pia mater diseases detected by CT or MRI at screening time (patients
             with stable symptoms and complete treatment 14 days before enrollment may be admitted
             to the group, but no symptoms of cerebral hemorrhage should be confirmed by
             craniocerebral MRI, CT or venography evaluation).

          -  Uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg, or diastolic blood
             pressure ≥ 90 mmHg, despite using the optimal medical treatment;

          -  Patients are participating in other clinical studies, or there are less than four
             weeks before the end of the previous clinical study.

          -  Other active malignant tumors requiring concurrent treatment;

          -  The patient has a history of malignant tumors. Patients with basal cell carcinoma of
             skin, superficial bladder cancer, squamous cell carcinoma of skin or carcinoma of
             cervix in situ who had undergone possible curative treatment and had no disease
             recurrence within 5 years after the initiation of curative treatment are permitted.

          -  Patients had treatment related adverse reactions after previous systemic anti-tumour
             therapy (except hair loss), but did not recover to NCI-CTCAE ≤ 1 grade.

          -  The patient has the coagulation disorders (INR > 1.5 or prothrombin time (PT) > ULN +
             4 seconds or activated partial thromboplastin time (APTT) > 1.5 ULN), or bleeding
             tendency, or undergoing thrombolysis or anticoagulation therapy; Note: On the premise
             that the International Standardized Ratio of Prothrombin Time (INR) is less than 1.5,
             low doses of heparin (0.6 million to 12,000 U per day for adults) or aspirin (less
             than 100 mg per day) are allowed for preventive purposes.

          -  Renal insufficiency: Urinary routine indicated that urinary protein ≥ ++ or confirmed
             24-hour urinary protein ≥ 1.0 g;

          -  Subjects who had undergone major surgery or had severe trauma had less than 14 days
             before enrollment.

          -  Severe acute or chronic infections requiring systemic treatment

          -  Severe cardiovascular diseases: grade II or above myocardial ischemia or myocardial
             infarction and poor control arrhythmias (including corrected QT interval (QTc)
             interval ≥ 450 ms for males and ≥ 470 ms for females); cardiac insufficiency of grade
             III to IV according to New York Heart Association (NYHA) criteria, or left ventricular
             ejection fraction (LVEF) < 50% by color Doppler echocardiography;

          -  ≥ CTCAE grade 2 peripheral neuropathy, except for trauma.

          -  Respiratory syndrome (≥ CTCAE grade 2 dyspnea), serous effusion (including pleural
             effusion, ascites, pericardial effusion) requiring surgical treatment;

          -  Long-term unhealed wound or fracture;

          -  Decompensated diabetes mellitus or other contraindications of high-dose glucocorticoid
             therapy;

          -  There are obvious factors affecting oral drug absorption, such as inability to
             swallow, chronic diarrhea and intestinal obstruction;

          -  Three months prior to enrollment, significant hemoptysis (more than 50 ml per day)
             occurred, or significant clinical hemorrhage symptoms or defined bleeding tendency,
             such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult
             blood ++ or above, or suffering from vasculitis.

          -  Arteriovenous thrombosis events occurred within 12 months before enrollment, such as
             cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage,
             cerebral infarction), deep vein thrombosis and pulmonary embolism.

          -  Patients participated in clinical trials of other antineoplastic drugs within four
             weeks prior to enrollment, or planned systemic anti-tumor therapy within four weeks
             prior to enrollment or during the period of the study, including cytotoxic therapy,
             signal transduction inhibitors, immunotherapy (or use of mitomycin C within six weeks
             prior to the treatment of the experimental drugs). Over-extended-field radiotherapy
             (EF-RT) was performed within four weeks prior to grouping or limited-field
             radiotherapy to evaluate the tumor lesions was performed within two weeks prior to
             grouping;

          -  Physical and laboratory findings Untreated active hepatitis (hepatitis B: HBsAg
             positive and hepatitis B virus (HBV) DNA ≥ 500 IU/mL; hepatitis C: hepatitis C virus
             (HCV) RNA positive and abnormal liver function); co-infection of hepatitis B and
             hepatitis C;

          -  According to the researcher's judgment, patients may have other factors that may lead
             to the forced termination of the study, such as other serious diseases or serious
             abnormal laboratory examinations or other factors that may affect the safety of the
             subjects, or family or social factors such as test data and sample collection.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival(PFS)
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:6 months and 12 months progression-free survival (PFS) Rate
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:objective response rate (ORR)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Disease Control Rate(DCR)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From the date of randomization to the date of death from any cause,assessed up to 2 year
Safety Issue:
Description:
Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:Up to 21 days post-the last treatment
Safety Issue:
Description:Adverse Events
Measure:progression-free survival (PFS) for different types of EGFR mutation
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Overall survival (OS) for different types of EGFR mutation
Time Frame:Up to 2 year
Safety Issue:
Description:

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Guangdong Association of Clinical Trials

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