Clinical Trials /

Apatinib Combine With EGFR-TKI for Advanced EGFR-TKI-resistant Non-Small Cell Lung Cancer

NCT03050411

Description:

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib demonstrate excellent effect on the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, patients who are initially sensitive to the drugs eventually become resistance. Apatinib is a highly selective VEGFR2 inhibitor and reduces the angiogenesis of tumor efficiently. In this study, the investigators aim to explore the efficacy and reasonable dosage of apatinib combining with EGFR-TKI in advanced non-squamous non-small cell lung cancer with EGFR-TKI resistance.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Apatinib Combine With EGFR-TKI for Advanced EGFR-TKI-resistant Non-Small Cell Lung Cancer
  • Official Title: A Study of Apatinib Combine With EGFR-TKI for Advanced EGFR-TKI-resistant Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00006761-2016162
  • NCT ID: NCT03050411

Conditions

  • Nonsmall Cell Lung Cancer

Interventions

DrugSynonymsArms
Apatinib Mesylate TabletsApatinib
EGFR-TKIs (Erlotinib, Gefitinib and Osimertinib)Apatinib

Purpose

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib demonstrate excellent effect on the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, patients who are initially sensitive to the drugs eventually become resistance. Apatinib is a highly selective VEGFR2 inhibitor and reduces the angiogenesis of tumor efficiently. In this study, the investigators aim to explore the efficacy and reasonable dosage of apatinib combining with EGFR-TKI in advanced non-squamous non-small cell lung cancer with EGFR-TKI resistance.

Detailed Description

      Primary Outcome Measure: efficacy and reasonable dosage of the combination of apatinib and
      EGFR-TKI in advanced non-squamous non-small cell lung cancer with EGFR-TKI resistance.

      Secondary Outcome Measures: Progression free survival, overall survival, Side effects.
    

Trial Arms

NameTypeDescriptionInterventions
ApatinibExperimentalApatinib in combination with EGFR-TKIs
  • Apatinib Mesylate Tablets
  • EGFR-TKIs (Erlotinib, Gefitinib and Osimertinib)

Eligibility Criteria

        Inclusion Criteria:

          1. Obtain of informed consent.

          2. Histologically or cytologically confirmed, inoperable, recurrence or metastasis
             advanced non-small cell lung cancer (TNM Stage ⅢB or stage Ⅳ), took EGFR-TKI longer
             than 6 months and appeared disease progression.

          3. At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the
             requirements of the standard Response Evaluation Criteria In Solid Tumors(RESCIST)
             version 1.1).

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

          5. Aged from 18 to 75 years (18 and 75 years are included).

          6. Life expectancy ≥12 weeks.

          7. Adequate bone marrow reserve and organ function as follows:

               -  Absolute neutrophils count (ANC) ≥1.5 x 10 to the 9th power/L (band neutrophil
                  and segmented neutrophil), platelets > 100 x 10 to the 9th power/L and Hb≥90g/L.

               -  Hepatic: total bilirubin less than or equal to 1.5 times upper limit of normal
                  (ULN).

               -  Alkaline phosphatase (AP), alanine transaminase (ALT) and aspartate transaminase
                  (AST) less than or equal to 3.0 times ULN (or less than or equal to 5 times ULN
                  in case of known liver involvement.

               -  Renal: Serum Creatinine less than or equal to 1.25 times upper limit of normal
                  (ULN).

          8. Have history of hypertension (less than 135/85mmHg).

          9. Females of child-bearing potential must have negative serum pregnancy test. Sexually
             active males and females (of childbearing potential) willing to practice contraception
             during the study.

        Exclusion Criteria:

          1. Do not meet the above criteria.

          2. Prior treatment with VEGFR tyrosine kinase inhibitors or VEGFR targeting agent.

          3. Unhealed toxicity of prior anti-cancer treatment (CTCAE Level 1) or surgery.

          4. Symptomatic Central Nervous System (CNS) metastases.

          5. Uncontrolled hypertension (systolic ≥140mmHg and/or diastolic ≥90mmHg after medication
             treatment).

          6. Clinical uncontrolled active infection, such as acute pneumonia, active hepatitis B or
             C (prior hepatitis B history, despite medication treatment control or not, HBV
             DNA≥500copies or ≥100IU/ml), etc.

          7. Arterial thrombosis or venous thrombosis in 6 months, or disposition evidence of
             thrombosis/bleeding in 2 month (despite severity), hemoptysis in 2 weeks (bright red
             blood, 1/2 teaspoon).

          8. Stroke or transient ischemic attack (TIA) in 12 month.

          9. Unhealed skin lesions, surgical site, injuries, severe mucous membrane ulcer or bone
             fracture.

         10. Cardiac function evaluation: LVEF <50%, a recent history of MI in 6 months,
             severe/unstable angina or coronary bypass surgery, or cardiac insufficiency ≥ NYHA 2.

         11. Prior other malignant disease in 5 years (except carcinoma in situ of cervix, or non
             melanoma skin cancers, or localized prostate cancer with Gleason ≤6).

         12. Documented history of neurological or psychiatric disorders, include epilepsy and
             dementia.

         13. Recent active digestive disease such as duodenal ulcers, ulcerative colitis, ileus,
             ect., intestinal perforation, intestine fistula, or other conditions may lead to
             gastrointestinal bleeding or perforation which regimented at investigators'
             discretion.

         14. Difficulty swallowing or known malabsorption.

         15. A history of organ transplantation and long-term immunosuppressive medication.

         16. Take part in new drug clinical trials within one month or taking part in a trial now.

         17. Pregnant or lactating woman.

         18. A history of anaphylaxis of apatinib analogue and/or excipient of drugs in this study.

         19. Other conditions regimented at investigators' discretion.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Optimal Dosage
Time Frame:9 months
Safety Issue:
Description:Optimal dosage of Apatinib which combine with EGFR-TKIs

Secondary Outcome Measures

Measure:Overall survival
Time Frame:24 months
Safety Issue:
Description:Overall survival is evaluated in the 24th month since the treatment began
Measure:Side effects
Time Frame:24 months
Safety Issue:
Description:Side effects evaluated in the 24th month since the treatment began according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Peking University Third Hospital

Trial Keywords

  • Non Small Cell Lung Cancer
  • EGFR-TKI resistance
  • Apatinib
  • anti-angiogenesis drugs

Last Updated

February 9, 2017