Anti-angiogenesis Combine With EGFR-TKI in Advanced Non-squamous Non Small Cell Lung Cancer

Anti-angiogenesis Combine With EGFR-TKI in Advanced Non-squamous Non Small Cell Cancer

Epidermal growth factor receptor Tyrosine kinase inhibitor (EGFR TKI) have been approved to treat NSCLC harboring EGFR mutation as first-line therapy. However, the acquired resistance of EGFR-TKI is a common and severe problem.The study explore the superiority of anti-angiogenesis drugs (Apatinib, endostatin, anlotinib) plus EGFR TKI versus single EGFR-TKI.

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: EGFR-TK Inhibitor; Drug: Anti-Angiogenic Drugs

Detailed Description

Non-small-cell lung cancer (NSCLC) is the leading cause from cancer in China. Epidermal growth factor receptor Tyrosine kinase inhibitor (EGFR TKI) have been approved to treat NSCLC harboring EGFR mutation as first-line therapy. However, a large proportion of patients would become acquired resistant of EGFR-TKI after about one year although initially sensitivity. Anti-angiogenesis therapy plus EGFR-TKI has been demonstrated valid and safe in NSCLC patients. Apatinib, endostatin, anlotinib belong to anti-angiogenesis drugs and can inhibit tumor growth. In this study, we plan to recruit NSCLC patients who are assessed as stable disease ( according to RECIST) under treatment of EGFR-TKI. Then, these patients would be divided into two groups: single EGFR-TKI or EGFR-TKI plus anti-angiogenesis drugs. Progression free survival, overall survival and safety are our evaluation events.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: chen zhengtang, PhD; Phone Number: +86 02368755625; Email: wangjm1987@foxmail.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Xinqiao Hospital
      • Contact: cheng zheng tang, professor; Phone Number: UK 023-68755114; Email: wangjm1987@foxmail.com
      • Principal Investigator: ZhengTang Chen, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged from 18 to 75 years (18 and 75 years are included)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 2 months and appeared Stable disease.
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. Life expectancy ≥12 weeks.

6. 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).
7. 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. Unhealed toxicity of prior anti-cancer treatment (CTCAE Level 1) or surgery. Uncontrolled hypertension (systolic ≥140mmHg and/or diastolic ≥90mmHg after medication treatment).
3. 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.
4. 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).
5. Stroke or transient ischemic attack (TIA) in 12 month. Unhealed skin lesions, surgical site, injuries, severe mucous membrane ulcer or bone fracture.
6. 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.
7. Prior other malignant disease in 5 years.
8. 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.
9. Difficulty swallowing or known malabsorption.
10. A history of organ transplantation and long-term immunosuppressive medication.
11. Take part in new drug clinical trials within one month or taking part in a trial now.
12. Pregnant or lactating woman.
13. Other conditions regimented at investigators' discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EGFR-TKI plus anti-angiogenesis; EGFR-TKI(erlotinib or gefitinib) plus anti-angiogenesis(endostatin or apatinib or anlotinib)	Drug: EGFR-TK Inhibitor; EGFR-TKIs include but are not limited erlotinib, gefitinib; Drug: Anti-Angiogenic Drugs; Anti-Angiogenic Drugs contain endostatin, apatinib and anlotinib
Active Comparator: EGFR-TKI; EGFR-TKI(erlotinib or gefitinib)	Drug: EGFR-TK Inhibitor; EGFR-TKIs include but are not limited erlotinib, gefitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival(PFS)	PFS is evaluated in 24 months since the treatment begin	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (0S)	OS is evaluated in 24 months since the treatment begin	24 months

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2018
• Primary Completion (Anticipated): August 30, 2019
• Study Completion (Anticipated): February 20, 2020

Study Registration Dates

• First Submitted: March 4, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 8, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Angiogenesis Inhibitors
• Other Study ID Numbers: xinqiao2018001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No