Apatinib in the Treatment of Patients With EGFR T790M-Negative NSCLC

NCT ID: NCT03389256

Last Updated: 2018-01-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-30
• Study Completion Date: 2022-08-30

Brief Summary

This phase 2 study is designed to evaluate the safety and activity of apatinib,a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2, in combination with EGFR-TKI in NSCLC with T790M-negative after the failure of EGFR-TKI therapy.

Conditions

Lung Diseases; Neoplasms; Respiratory Tract Diseases; Thoracic Neoplasms; Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

apatinib combine with EGFR-TKI

Every 4 weeks 1 cycle, evaluated the efficacy and safety once every 2 cycles, treat until disease progression or intolerable toxicity

Group Type: EXPERIMENTAL

Apatinib

Intervention Type: DRUG

Apatinib mesylate tablets 250 mg qd po, if the patient can tolerate the toxic side effects, adjust the dose to 500mg qd po after 1 week.

EGFR-TKI

Intervention Type: DRUG

Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po

EGFR-TKI

Every 4 weeks 1 cycle, evaluated the efficacy and safety once every 2 cycles, treat until disease progression or intolerable toxicity

Group Type: ACTIVE_COMPARATOR

EGFR-TKI

Intervention Type: DRUG

Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po

Interventions

Apatinib

Apatinib mesylate tablets 250 mg qd po, if the patient can tolerate the toxic side effects, adjust the dose to 500mg qd po after 1 week.

Intervention Type: DRUG

EGFR-TKI

Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po

Intervention Type: DRUG

Other Intervention Names

apatinib tablets; Imatinib、Gefitinib or Erlotinib

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed stage IIIB, IV non-squamous non-small cell lung cancer, with measurable lesions (the long axis of tumor lesions ≥ 10mm with CT, the short axis of lymph node lesions ≥ 15mm with CT, the lesions not receive radiotherapy, frozen or other local treatment);
• Patients with slow progression on first-line EGFR TKI(erlotinib / icotinib / gefitinib) treatment;
• No T790M mutation including an assessment from tumor biopsy obtained while on or subsequent to the most recent EGFR TKI therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
• Life expectancy of more than 3 months;
• Adequate bone marrow function: WBC ≥ 3.0 ×10 E+9/L, neutrophil ≥ 1.5 × 10 E+9/L, platelets ≥ 80 × 10E+9/L,Hb ≥ 10.0g/dL;a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL), a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤3UNL or ≤5UNL in case of liver metastasis, a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault);
• Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug;
• the participants volunteered to join this study should sign the informed consent forms, have better compliance in the follow-up;

Exclusion Criteria

• Squamous cell carcinoma (including adenosquamous carcinoma); Small cell lung carcinoma (including small cell carcinoma and non-small cell mixed lung carcinoma);
• Active brain metastases, cancerous meningitis, patients with spinal cord compression;
• Rapid progression of the disease or cancer invades vital organs;
• The distance between the tumor lesion and the large blood vessel is less than 5 mm, or there is a central tumor invading local macrovascular;
• obvious pulmonary cavity or tumor necrosis;
• Uncontrollable high blood pressure;
• Grade Ⅱ or above myocardial ischemia or myocardial infarction or arrhythmia control is not good,Ⅲ ~ Ⅳ grade cardiac insufficiency, or cardiac ultrasonography showed left ventricular ejection fraction (LVEF) <50% according to the NYHA standard;
• Have a history of interstitial lung disease or patients with interstitial lung disease;
• Coagulation abnormalities (INR> 1.5 or PT> ULN + 4s or APTT> 1.5 ULN) with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
• There was significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above;
• A clinically significant bleeding symptom or bleeding tendencies such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above, or vasculitis that occurred within 3 months prior to enrollment;
• Aneurysm / venous thrombotic events such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
• Arterial / venous thrombotic events such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months prior to enrollment;
• Hereditary or acquired bleeding and thrombophilia, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism；
• Long-term unhealed wounds or fractures;
• Major surgery or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment;
• Unable to swallow, chronic diarrhea or intestinal obstruction;
• Abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months prior to enrollment;
• Urinary protein ≥ ++, 24-hour urinary protein ≥ 1.0 g;
• Active infections require antimicrobial treatment;
• ALK gene abnormalities (gene fusion or mutation occurred);
• Pregnant or lactating women, or women unwilling or unable to take effective contraception;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sichuan Cancer Hospital and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Juan LI, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sichuan Cancer Hospital

Chengdu, Sichuan, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Sichuan Provincial People's Hospital

Chengdu, Sichuan, China

Countries

China

Central Contacts

Juan Li, MD

Role: CONTACT

dr.lijuan@gmail.com

+8613880276636

Rui Shi, MD

Role: CONTACT

shirui729@hotmail.com

+8613880898008

Facility Contacts

Panwen Tian, MD

Role: primary

+8618036675920

Rui Ao, MD

Role: primary

aorui1040@hotmail.com

+8618036675290

Other Identifiers

APTN-NSCLC-201712

Identifier Type: -

Identifier Source: org_study_id