Gefitinib With Anlotinib in Advanced Non-squamous NSCLC Patients With Uncleared Plasma ctDNA EGFRm After First-line Treatment With Gefitinib

April 21, 2020 updated by: Second Affiliated Hospital of Nanchang University

A Randomized Phase II Trial of Gefitinib With Anlotinib in Advanced Non-squamous NSCLC Patients With Uncleared Plasma ctDNA EGFRm After First-line Treatment With Gefitinib

TKIs therapy is the first-line treatment of patients with EGFR mutation advanced NSCLC.However, some patients have poor prognosis of drug resistance in the early stage. The dynamic alterations of ctDNA-based EGFR mutation after TKIs treatment is a predictor of the efficacy of TKIs treatment, which can be used to identify this part of patients in the early stage.Drug resistance can be overcome when TKIs is combined with drugs in different mechanisms of action, such as chemotherapy and anti-angiogenesis therapy.Gefitinib is the first-generation oral EGFR TKIs. Anlotinib is a domestic oral small molecule inhibitor of multireceptor tyrosine kinase, which has extensive inhibitory effect on tumor angiogenesis and growth.Gefitinib combined with anlotinib is a new option in the treatment of patients with uncleared plasma EGFRm after gefitinib treatment.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, prospective, randomized, controlled phase II clinical trial.To evaluate the efficacy and safety of gefitinib combined with anlotinib versus gefitinib alone in advanced non-squamous NSCLC patients whose EGFRm was not cleared in plasma ctDNA after 8 weeks of gefitinib first-line treatment, so as to provide clinical basis for a new and tolerable treatment that can prolong the survival time of patients with advanced NSCLC. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent. The efficacy and adverse reactions of the trial regimen will be evaluated according to RECIST criteria and NCI-CTC AE V3.0.

Study Type

Interventional

Enrollment (Anticipated)

240

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • The Second Afiliated Hospital of Nanchang University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed that EGFR sensitive mutation (ex19del or L858R mutation) in tumor tissue was detected by non-squamous NSCLC, and EGFR mutation (ex19del or L858R mutation) in ctDNA before treatment;
  • Staging is IVB stage (AJCC 8th Edition) ;
  • According to the comprehensive judgment of many disciplines, it is impossible to be treated by operation;
  • PS score 0-1;
  • The patient has at least one measurable tumor injury (the tumor is considered unmeasurable at the site of previous radiotherapy);
  • Systemic anti-tumor therapy such as chemotherapy, immunotherapy and targeted therapy were not performed before entering the group;
  • There is no history of malignant tumor and no serious medical disease;
  • FEV1 ≥ 1.2L/ seconds or ≥ 50% predicted value;
  • Laboratory examination: White blood cell count ≥ 4 *10^9/L, neutrophil count ≥ 2.0 *10^9, platelet count ≥ 100 *10^9, hemoglobin ≥ 10 g / L, liver and kidney function and ECG were normal;
  • The pregnancy test was negative within 3 days before entering the group, and agreed to use medically effective contraceptive measures during the trial;
  • Life expectancy is more than 12 weeks;
  • Sign informed consent form; cooperate with regular follow-up.

Exclusion Criteria:

  • T4 (AJCC 8th Edition) patients with severe destruction and stenosis of large vessels confirmed by imaging;
  • Clinical severe infection (> grade 2 NCI-CTC V3.0);
  • Severe immunosuppressive disease;
  • The patient's physical condition is life-threatening;
  • A pregnant or breastfeeding patient. Female patients who are likely to become pregnant must be tested negative within 7 days of the start of treatment before continuing. Patients enrolled in the trial (both male and female) must use contraception during the trial period until two weeks after the trial is completed;
  • PS score ≥ 2;
  • At the same time, there are other serious diseases (congestive heart failure, transmural myocardial infarction, COPD or other respiratory diseases that affect treatment, etc.), considering that the study may aggravate or fail to control the disease;
  • Those who have suffered or are currently suffering from tumors whose primary site or histology are different from those evaluated in this study. Excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder surface tumor [Ta,Tis&T1], or any cured tumor that has been in the study for more than 3 years;
  • The patient refused to participate.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Gefitinib with Anlotinib
If persistence of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment, Gefitinib 250mg oral daily and Anlotinib 10mg oral d1-14, every 3 weeks
Drug: Gefitinib
If persistence of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment
Other Names:
  • Iressa
Drug: Anlotinib
If clearance of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment
Other Names:
  • AL3818
EXPERIMENTAL: Gefitinib
If clearance of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment, Gefitinib 250mg oral daily
Drug: Gefitinib
If persistence of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment
Other Names:
  • Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival, PFS
Time Frame: Every 6 weeks up to 2 years
The period from the start of treatment to the progression or death of a patient
Every 6 weeks up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival, OS
Time Frame: Every 6 weeks up to 2 years, and then every 3 months up to 5 years
time from the beginning of study to death due to any cause or last follow-up
Every 6 weeks up to 2 years, and then every 3 months up to 5 years
Objective Response Rate, ORR
Time Frame: 6 weeks after treatment
ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)
6 weeks after treatment
adverse events
Time Frame: Every 6 weeks up to 2 years
Number of patients with adverse events (AEs) as a measure of safety and tolerability
Every 6 weeks up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital of Nanchang University

Collaborators

Nanchang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

May 1, 2020

Primary Completion (ANTICIPATED)

May 1, 2022

Study Completion (ANTICIPATED)

November 1, 2022

Study Registration Dates

First Submitted

April 21, 2020

First Submitted That Met QC Criteria

April 21, 2020

First Posted (ACTUAL)

April 24, 2020

Study Record Updates

Last Update Posted (ACTUAL)

April 24, 2020

Last Update Submitted That Met QC Criteria

April 21, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20171BCD40022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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