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

Sponsor

Sichuan Cancer Hospital and Research Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03389256

Collaborator

Jiangsu HengRui Medicine Co., Ltd. (Industry)

144

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Diseases Neoplasms Respiratory Tract Diseases Thoracic Neoplasms Non-Small-Cell Lung	Drug: Apatinib Drug: EGFR-TKI	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Controlled Phase II Clinical Trial of Apatinib in Combination With EGFR-TKI Versus EGFR-TKI for Non-squamous, Non-small Cell Lung Cancer(NSCLC) With T790M-negative After the Failure of EGFR-TKI Therapy

Anticipated Study Start Date :

Dec 30, 2018

Anticipated Primary Completion Date :

Dec 30, 2020

Anticipated Study Completion Date :

Aug 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: 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. Other Names: apatinib tablets Drug: EGFR-TKI Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po Other Names: Imatinib、Gefitinib or Erlotinib
Active Comparator: EGFR-TKI Every 4 weeks 1 cycle, evaluated the efficacy and safety once every 2 cycles, treat until disease progression or intolerable toxicity	Drug: EGFR-TKI Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po Other Names: Imatinib、Gefitinib or Erlotinib

Arm

Intervention/Treatment

Experimental: 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

Drug: 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.

Other Names:

apatinib tablets

Drug: EGFR-TKI

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

Other Names:

Imatinib、Gefitinib or Erlotinib

Active Comparator: EGFR-TKI

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

Drug: EGFR-TKI

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

Other Names:

Imatinib、Gefitinib or Erlotinib

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [up to 24 months]
the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse

Secondary Outcome Measures

Overall survival (OS) [up to 36 months]
The length of time from either the date of diagnosis or the start of treatment that half of the patients in a group of patients diagnosed with the disease are still alive.
Duration of response (DOR) [up to 24 months]
From first response to the date of first documented disease progression
Disease Control Rate (DCR) [24 weeks]
the proportion of patients with a best overall response of CR, PR or SD in the whole body, as assessed per RECIST 1.1 by the investigator.
Overall response rate (ORR) [24 weeks]
the proportion of patients with a best overall confirmed response of CR or PR in the whole body as assessed per RECIST 1.1 by the investigator
the quality of life (QoL) [up to 36 months]
Analysis of changes from baseline using the quality of life (QoL) instrument

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sichuan Cancer Hospital	Chengdu	Sichuan	China	610041
2	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
3	Sichuan Provincial People's Hospital	Chengdu	Sichuan	China	610071