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

NCT03050411 | Unknown Phase 1

• 1 other identifier: IRB00006761-2016162
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nonsmall Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Optimal Dosage

  Optimal dosage of Apatinib which combine with EGFR-TKIs

  9 months

• Progression free survival

  PFS is evaluated in 24 months since the treatment begin

  24 months

Secondary Outcomes (2)

• Overall survival

  24 months

• Side effects

  24 months

Study Arms (1)

Apatinib

EXPERIMENTAL

Apatinib in combination with EGFR-TKIs

Drug: Apatinib Mesylate Tablets; Drug: EGFR-TKIs (Erlotinib, Gefitinib and Osimertinib)

Interventions

Apatinib Mesylate Tablets DRUG

250mg, 500mg, 750mg, q.d., p.o.

Apatinib

EGFR-TKIs (Erlotinib, Gefitinib and Osimertinib) DRUG

EGFR-TKIs include but are not limited erlotinib, gefitinib and osimertinib

Apatinib

Eligibility Criteria

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

You may qualify if:

• Obtain of informed consent.
• 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.
• 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).
• Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2.
• Aged from 18 to 75 years (18 and 75 years are included).
• Life expectancy ≥12 weeks.
• 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).
• Have history of hypertension (less than 135/85mmHg).
• 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.

You may not qualify if:

• Do not meet the above criteria.
• Prior treatment with VEGFR tyrosine kinase inhibitors or VEGFR targeting agent.
• Unhealed toxicity of prior anti-cancer treatment (CTCAE Level 1) or surgery.
• Symptomatic Central Nervous System (CNS) metastases.
• Uncontrolled hypertension (systolic ≥140mmHg and/or diastolic ≥90mmHg after medication treatment).
• 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.
• 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).
• Stroke or transient ischemic attack (TIA) in 12 month.
• Unhealed skin lesions, surgical site, injuries, severe mucous membrane ulcer or bone fracture.
• 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.
• 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).
• Documented history of neurological or psychiatric disorders, include epilepsy and dementia.
• 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.
• Difficulty swallowing or known malabsorption.
• A history of organ transplantation and long-term immunosuppressive medication.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

apatinib; Erlotinib Hydrochloride; Gefitinib; osimertinib

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Li Liang, Prof. M.D.

  Peking University Third Hospital

  STUDY CHAIR

Central Study Contacts

Li Liang, Prof. M.D.

CONTACT

liang.dr@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. M.D.

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: February 10, 2017
• Study Start: May 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: October 1, 2019
• Last Updated: February 10, 2017

Record last verified: 2017-02

Locations

CN (1)