Study of Anlotinib Combined With Icotinib as the First-line Treatment in Patients With EGFR Mutation-positive NSCLC

NCT03736837 | Completed Phase 2 DMC

• 1 other identifier: ALTER-L004
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

Evaluate the efficacy and safety of Anlotinib plus Icotinib as the first-line treatment in patients with sensitive EGFR mutations advanced non-small cell lung cancer.

Conditions

Non Small Cell Lung Cancer

Keywords

sensitive EGFR mutations; anlotinib; icotinib; first line; cancer; non-squamous NSCLC

Outcome Measures

Primary Outcomes (1)

• PFS（Progress free survival）

  The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

  each 42 days up to PD or death (up to 24 months)

Secondary Outcomes (4)

• OS（Overall Survival）

  From enrollment until death (up to 24 months)

• ORR（Objective Response Rate）

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• DCR（Disease Control Rate）

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• Adverse Events

  Until 30 day safety follow-up visit

Study Arms (1)

Anlotinib Plus Icotinib

EXPERIMENTAL

Anlotinib 12 mg once a day from day 1 to 14 of a 21-day cycle. Icotinib 125mg p.o, tid. It should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent.

Drug: Anlotinib Plus Icotinib

Interventions

Anlotinib Plus Icotinib DRUG

Anlotinib：12mg/capsule, take once when limosis in the morning. If patients suffer from AEs, they can get declined dosage (10mg or 8mg). Icotinib：125 mg/tablet，three times a day，fasting or serving with food. It should be continued until disease progression or intolerable toxicity or patients withdraw of consent.

Also known as: A+T

Anlotinib Plus Icotinib

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent
• years，ECOG PS：0-2，Life expectancy of more than 3 months，with measurable lesion ( RECIST1.1)
• Histologically or cytologically confirmed, locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC or recurrent non-squamous NSCLC（according to the 8th Edition of the AJCC Staging system）with EGFR 19 del and/or 21 L858R gene mutation
• Has not received chemotherapy or other targeted therapies；For recurrent disease, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant chemotherapy may be accepted, but recurrence occurs after ≥6 months from stopping treatment.
• ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction；Previously received radiation therapy, but the radiotherapy area must be \<25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment;
• Main organs function is normal
• Patients of brain metastases with asymptomatic or mild symptoms can be enrolled
• The woman patients of childbearing age must agree to take contraceptive methods during the research and within another 8 weeks after treatment. Pregnancy test (blood serum test or urine) should be done within 7 days before the research and the result should be negative.The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after treatment.

You may not qualify if:

• Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
• ALK-positive NSCLC
• Central Lung tumors that Imaging (CT or MRI) shows tumor lesions invade local large blood vessels; or with significant pulmonary cavum or necrotizing
• Patients with obvious brain metastases, cancerous meningitis, spinal cord compression, or with brain or pia mater disease. (patient with brain metastases who have completed treatment 14 days before and the symptoms are stable can be Enrolled, also should have no cerebral hemorrhage symptoms confirmed by brain MRI, CT or venography evaluation
• The patient is participating in other clinical studies or Participated in other anti-tumor drug clinical trials within 4 weeks before enrollment
• With other active malignancies that require simultaneous treatment
• Has a history of malignant tumors. Except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone curative treatment and have no disease recurrence within 5 years after the start of treatment
• Patients with adverse reactions derived from previous therapies (excluding hair loss), which is over level 1 in CTC AE (4.0)
• abnormal blood coagulation (INR\>1.5 or PT \> ULN + 4s or APTT \> 1.5 ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy
• renal insufficiency: urinary protein ≥ ++, or 24-hour urine protein ≥ 1.0g;
• The effect of surgery or trauma has been eliminated for less than 14 days before enrollment
• Severe acute or chronic infections requiring systemic treatment
• Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias
• Patients with peripheral neuropathy which is over level 2 in CTC AE (4.0), except for trauma
• respiratory syndrome (dyspnea≥CTC AE 2), severe pleural effusion, ascites, pericardial effusion

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (5)

Hebei Provincial People's Hospital

Shijiazhuang, Hebei, China

Location

Neimenggu Autonomous Region People's Hospital

Hohhot, Neimenggu, China

Location

Neimenggu Medical University Affiliated Hospital

Hohhot, Neimenggu, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, China

Location

Related Publications (2)

• Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.

  PMID: 25175099 RESULT

• Zhang L, Wang L, Wang J, Chen J, Meng Z, Liu Z, Jiang X, Wang X, Huang C, Chen P, Liang Y, Jiang R, Wang J, Zhong D, Shang Y, Zhang Y, Zhang C, Huang D. Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study. Mol Cancer. 2023 Aug 5;22(1):124. doi: 10.1186/s12943-023-01823-w.

  PMID: 37543587 DERIVED

Related Links

• Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567): Updated Safety Results
• NEJ026: Phase III study comparing bevacizumab plus erlotinib to erlotinib in patients with untreated NSCLC harboring activating EGFR mutations
• Phase III study comparing bevacizumab plus erlotinib (BE) to erlotinib (E) in patients (pts) with untreated NSCLC harboring EGFR mutations: NEJ026

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

anlotinib; icotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Dingzhi Huang, Doctor

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 9, 2018
• Study Start: December 1, 2018
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: March 15, 2021

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 6 months of study completion
• Access Criteria: Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.

Locations

CN (5)