Anlotinib Hydrochloride Combined With EGFR-Tyrosine Kinase Inhibitor (TKI) in Treating Advanced NSCLC Patients With Acquired Resistance to EGFR-TKI

NCT04007835 | Unknown

• 1 other identifier: CTONG1803
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The Single-arm, multicenter study evaluate the safety and efficacy of Anlotinib Hydrochloride combined with EGFR TKIs in treating Advanced NSCLC With acquired Resistance to EGFR TKIs

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression free survival（PFS）

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year

Secondary Outcomes (7)

• 6 months and 12 months progression-free survival (PFS) Rate

  Up to 1 year

• objective response rate (ORR)

  Up to 1 year

• Disease Control Rate(DCR)

  Up to 1 year

• Overall survival (OS)

  From the date of randomization to the date of death from any cause，assessed up to 2 year

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Up to 21 days post-the last treatment

Study Arms (1)

Anlotinib Hydrochloride combined with EGFR-TKI

EXPERIMENTAL

Patients receive anlotinib (12 mg orally daily for 14 days every 21 days cycle) combined with one of following EGFR-TKIs: Gefitinib is administered 250 mg once per day. Erlotinib is administered 150 mg once per day , or Icotinib is administered 125 mg three times per day, until disease progression or untolerated toxicity.

Drug: Anlotinib Hydrochloride

Interventions

Anlotinib Hydrochloride DRUG

anlotinib (12 mg orally daily for 14 days every 21 days cycle) combined with one of EGFR-TKIs

Also known as: Gefitinib Tablets, Erlotinib Hydrochloride Tablets, Icotinib Hydrochloride Tablets

Anlotinib Hydrochloride combined with EGFR-TKI

Eligibility Criteria

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

You may qualify if:

• Patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up;
• Males or females aged 18 Years to 75 Years
• The patients should be confirmed with EGFR mutation \[e.g., T 790 M , exon 19 deletion, L 858 R, etc\],
• Cytologically or histologically confirmed locally advanced and / or metastatic non-small cell lung cancer (NSCLC).
• Patients should be using the EGFR TKI monotherapy as the first line treatment and meet the following criteria:
• Patients who showed objective clinical benefit from treatment with an EGFR
• TKI as defined by either:
• Patients who showed complete (CR) or partial response (PR) ≥ 4 months, or
• Patients who maintained stable disease (SD) status ≥ 6 months
• Patients who showed 1. risk of recurrence and progression, 2. gradual progression or local progression while on continuous treatment with EGFR TKI within the last 28 days prior to enrollment.( For recurrent diseases, patients can be accepted with adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant chemotherapy in the past, and 3. relapse occurs 6 months after the end of treatment).
• CEA≥10ng/ml；
• Gradual progression: Disease control lasting ≥6 months with EGFR-TKI treatment, Compared with the previous assessment, no significant increment of tumor burden and progressive involvement of non-target lesions with a score less than 2, and Symptom scored ≤1. Local progression: Disease control lasting more than 3 months with EGFR-TKI treatment, Progressive disease (PD) due to solitary extracranial lesion or limitation in intracranial lesions (covered by a radiation field),and symptom scored ≤1
• Evidence of imaging or clinical progression is required if progression of disease occurs during the treatment or after the last treatment.
• At least one measurable lesion meet the requirements of the standard Response Evaluation Criteria In Solid Tumors（RESCIST）version 1.1
• Life expectancy is at least 3 months;

You may not qualify if:

• Small cell lung cancer (including Small cell lung cancer mixed with non-small cell lung cancer);
• Imaging (CT or MRI) showed that the distance between the lesion and the large vessels was less than 5 mm, or there were central tumors invading the local large vessels, or there were obvious pulmonary cavity or necrotic tumors.
• Patients with active brain metastasis, cancerous meningitis, spinal cord compression, or with brain or pia mater diseases detected by CT or MRI at screening time (patients with stable symptoms and complete treatment 14 days before enrollment may be admitted to the group, but no symptoms of cerebral hemorrhage should be confirmed by craniocerebral MRI, CT or venography evaluation).
• Uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg, or diastolic blood pressure ≥ 90 mmHg, despite using the optimal medical treatment;
• Patients are participating in other clinical studies, or there are less than four weeks before the end of the previous clinical study.
• Other active malignant tumors requiring concurrent treatment;
• The patient has a history of malignant tumors. Patients with basal cell carcinoma of skin, superficial bladder cancer, squamous cell carcinoma of skin or carcinoma of cervix in situ who had undergone possible curative treatment and had no disease recurrence within 5 years after the initiation of curative treatment are permitted.
• Patients had treatment related adverse reactions after previous systemic anti-tumour therapy (except hair loss), but did not recover to NCI-CTCAE ≤ 1 grade.
• The patient has the coagulation disorders (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or activated partial thromboplastin time (APTT) \> 1.5 ULN), or bleeding tendency, or undergoing thrombolysis or anticoagulation therapy; Note: On the premise that the International Standardized Ratio of Prothrombin Time (INR) is less than 1.5, low doses of heparin (0.6 million to 12,000 U per day for adults) or aspirin (less than 100 mg per day) are allowed for preventive purposes.
• Renal insufficiency: Urinary routine indicated that urinary protein ≥ ++ or confirmed 24-hour urinary protein ≥ 1.0 g;
• Subjects who had undergone major surgery or had severe trauma had less than 14 days before enrollment.
• Severe acute or chronic infections requiring systemic treatment
• Severe cardiovascular diseases: grade II or above myocardial ischemia or myocardial infarction and poor control arrhythmias (including corrected QT interval (QTc) interval ≥ 450 ms for males and ≥ 470 ms for females); cardiac insufficiency of grade III to IV according to New York Heart Association (NYHA) criteria, or left ventricular ejection fraction (LVEF) \< 50% by color Doppler echocardiography;
• ≥ CTCAE grade 2 peripheral neuropathy, except for trauma.
• Respiratory syndrome (≥ CTCAE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Guangdong General Hospital

Guangzhou, Guangdong, 510080, China

Location

Related Publications (1)

• Chen HJ, Tu HY, Hu Y, Fan Y, Wu G, Cang S, Yang Y, Yang N, Ma R, Jin G, Xu X, Liu A, Tang S, Cheng Y, Yu Y, Xu CR, Zhou Q, Wu YL. A phase II trial of anlotinib plus EGFR-TKIs in advanced non-small cell lung cancer with gradual, oligo, or potential progression after EGFR-TKIs treatment (CTONG-1803/ALTER-L001). J Hematol Oncol. 2025 Jan 5;18(1):3. doi: 10.1186/s13045-024-01656-0.

  PMID: 39757186 DERIVED

MeSH Terms

Interventions

Gefitinib; Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

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

Study Officials

• Yi-Long Wu, MD

  Guangdong General Hospital (GGH)& Guangdong Academy of Medical Sciences

  STUDY CHAIR

• HUAJUN CHEN, MD

  Guangdong Provincial People's Hospital

  STUDY DIRECTOR

Central Study Contacts

HUAJUN CHEN, MD

CONTACT

0086-13710581145; chjdoctor@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 5, 2019
• Study Start: July 1, 2019
• Primary Completion: July 1, 2021
• Study Completion: December 1, 2021
• Last Updated: July 5, 2019

Record last verified: 2019-07

Locations

CN (1)