Gefitinib in Combination With Anlotinib or Placebo in Previously Untreated EGFR-mutant NSCLC

NCT04028778 | Unknown Phase 3

• 1 other identifier: 2018-FXY-134-内科
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

Brief Summary

Gefitinib is currently the standard-of-care for patients with activating-EGFR mutant advanced non-small cell lung cancer (NSCLC). However, \~30-40% patients are still nonresponsive, and experience significantly varying duration of response and survival rate. Anlotinib is an efficient multi-target tyrosine kinase inhibitor (TKI) that effectively block the migration and proliferation of endothelial cells and reduce tumor microvascular density by targeting VEGFRs, FGFRs, PDGFRs. It has been proved to be safe and effective in advanced lung cancer after second-line standard chemotherapy failure, which can significantly extend the survival of patients and approves as a third-line treatment for advanced NSCLC. Here, we prepared to evaluate whether the combination of gefitinb and anlotinib can preferably improved survival of untreated NSCLC with EGFR activating mutation.

Conditions

Lung Cancer, Nonsmall Cell

Outcome Measures

Primary Outcomes (1)

• Progress-free survival (PFS)

  Progression-Free Survival (PFS) as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)

  Approximately 2 Years

Secondary Outcomes (4)

• Overall Survival (OS)

  Approximately 5 Years

• Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]), as Assessed Using RECIST v.1.1

  Approximately 2 Years

• Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1

  Approximately 2 Years

• Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1

  Approximately 2 Years

Other Outcomes (1)

• Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score

  Approximately 2 Years

Study Arms (2)

Gefitinib + Anlotinib

EXPERIMENTAL

Patients will be treated with Gefitinib 250mg, p.o., qd and anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; take on an empty stomach (take at the same time every day as possible), every 3 weeks for a cycle.

Drug: Gefitinib; Drug: Anlotinib Hydrochloride

Gefitinib + Placebo

PLACEBO COMPARATOR

Patients will be treated with Gefitinib 250mg, p.o., qd and placebo to simulate anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; take on an empty stomach (take at the same time every day as possible), every 3 weeks for a cycle

Drug: Gefitinib; Other: Placebo

Interventions

Gefitinib DRUG

Gefitinib 250mg, p.o., qd, D1-D21; 3 weeks one cycle.

Also known as: Iressa

Gefitinib + Anlotinib; Gefitinib + Placebo

Anlotinib Hydrochloride DRUG

Anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; 3 weeks one cycle.

Gefitinib + Anlotinib

Placebo OTHER

Placebo simulating anlotinib hydrochloride capsule 12mg, p.o., qd, D1-D14; 3 weeks one cycle.

Gefitinib + Placebo

Eligibility Criteria

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

You may qualify if:

• ≥ 18 and ≤ 75 years of age
• Eastern Cooperative Oncology Group(ECOG)performance scale 0 - 1.
• Life expectancy of more than 3 weeks
• Histologically confirmed，locally advanced and/or metastatic non-squamous NSCLC of stage IIIB (unsuitable for radiotherapy) or IV or recurrent NSCLC with measurable lesion/ according to RECIST 1.1 which has not received radiotherapy or cryotherapy.
• Documented evidence of tumor harboring an activating EGFR mutation (exon19 del and L858R)
• None previous chemotherapy or targeted therapy. NOTE: neoadjuvant and/or adjuvant therapy is allowed which is completed before 6 months
• Prior radiation therapy is allowed if: 25% or less of total bone marrow had been irradiated,pelvis and chest had not been irradiated; at least 4 weeks have elapsed from the completion of radiation treatment, and the acute toxicity from radiation treatment had been recover; irradiated lesion is not including measurable lesions unless documented progress after radiation.
• Adequate hepatic, renal, heart, and hematologic functions (Absolute Neutrophil Count(ANC) ≥ 1.5×109/L, Platelet (PLT) ≥ 100×109/L, Hemoglobin(HB) ≥ 100 g/L, total bilirubin within 1.5×the upper limit of normal(ULN), and serum transaminase≤2.5×the Upper Limit Of Normal(ULN), serum creatine ≤ 1 x Upper Limit Of Normal(ULN), creatinine clearance rate ≥ 50ml/min
• For women of child-bearing age, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative. They will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men (previous surgical sterilization accepted), will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug.
• Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

You may not qualify if:

• small cell lung cancer (including small cell and non-small cell mixed lung cancer)
• Symptomatic brain metastases (Patients who have no symptoms and is not needed to receive therapy before 21 days may participate in this trial, but need to be confirmed by MRI\\CT or venography that no hematencephalon symptom)
• Radiologically documented evidence of tumor lesions from large vessels ≤ 5mm or major blood vessel invasion or encasement by cancer; Obvious cavity or necrosis formed in the tumor.
• \. hypertensive patients are in the combination therapy of two or more antihypertensive drugs.
• patients with positive T790M mutation by Gene detection.
• Patients who suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade III-IV cardiac insufficiency according to New York Heart Association(NYHA) criteria or echocardiography check: left ventricular ejection fraction (LVEF)\<50%;
• History of pulmonary interstitial diseases or concurrent pulmonary interstitial diseases.
• Coagulation disfunction（INR\>1.5 or PT\>Upper Limit Of Normal(ULN)+4s or Activated Partial Thromboplastin Time (APTT) \>1.5 Upper Limit Of Normal(ULN)）, hemorrhagic tendency or receiving the therapy of thrombolysis or anticoagulation
• Daily hemoptysis up to two teaspoons or more before enrollment
• History of clinically relevant major bleeding event=\<3 months (e.g. gastrointestinal hemorrhage, Hemorrhagic acne， bleeding gastric ulcer, occult blood test ≥ (++), and vasculitis ;
• Within 12 months before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack(TIA), hematencephalon, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
• Known inherited and acquired hemorrhagic and thromboplastic possibility (such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.)
• Long-term untreated wounds or fractures（in addition to tumor-induced pathological fractures）
• Within 4 weeks of major surgery and/or injures, fractures , ulceration
• Significant factors that influence the ingestion and absorption of medicine, (e.g. unable swallow, chronic diarrhea and intestinal obstruction);

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Cancer Center of Sun Yat-Sen University (CCSU)

Guangzhou, Guangdong, China

RECRUITING

Related Publications (1)

• Zhou HQ, Zhang YX, Chen G, Yu QT, Zhang H, Wu GW, Wu D, Lin YC, Zhu JF, Chen JH, Hu XH, Lan B, Zhou ZQ, Lin HF, Wang ZB, Lei XL, Pan SM, Chen LM, Zhang J, Kong TD, Yao JC, Zheng X, Li F, Zhang L, Fang WF. Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial. Signal Transduct Target Ther. 2024 Aug 13;9(1):215. doi: 10.1038/s41392-024-01927-9.

  PMID: 39134529 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib

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

Central Study Contacts

Wenfeng Fang, MD

CONTACT

020-87343822; fangwf@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Multicenter, Randomized, Double-Blind Study

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 23, 2019
• Study Start: April 10, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: November 8, 2019

Record last verified: 2019-11

Locations

CN (1)