Clinical trial NCT04762459: Efficacy and Safety of Almonertinib Combined With or Without Chemotherapy as an Adjuvant Treatment for Stage II-IIIA Non-small Cell Lung Carcinoma Following Complete Tumour Resection
Official title: Efficacy and Safety of Almonertinib Combined With or Without Chemotherapy as an Adjuvant Treatment for EGFR Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma Following Complete Tumour Resection: A Multicenter, Randomized Controlled, Open-label Clinical Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Non-small Cell Lung Carcinoma
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: Jiangsu Hansoh Pharmaceutical Co., Ltd.
name: GeneCast Biotechnology Co., Ltd.
First posted: 2021-02-21
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, open label, phase III study.

Detailed description: This is a multicenter, randomized, open label, phase III study assessing the efficacy and safety of Almonertinib combined with or without chemotherapy as an adjuvant treatment in patients with epidermal growth factor receptor (EGFR) mutation positive stage II-IIIA non-squamous NSCLC following complete tumour resection: Eligible patients will be randomized to receive either Almonertinib alone (110mg, po, once daily) or Almonertinib (110mg, po, once daily) plus pemetrexed (500mg/m2, iv) and cisplatin (500mg/m2, iv) or pemetrexed (500mg/m2, iv) plus cisplatin (500mg/m2, iv) in a 3:2:1 ratio.

Eligibility criteria: Inclusion Criteria:

* Any patient who meets all of the following inclusion criteria will qualify for entry into the study:

  1. Male or female, aged at least 18 years.
  2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology.
  3. Brain examination must be done prior to surgery as it is considered standard of care.
  4. Patients must be classified post-operatively as Stage II-IIIA on the basis of pathologic criteria.
  5. Confirmation by the central laboratory that the tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M.
  6. Providing paraffin embedded section(10-15sheets),wax blocks or fresh frozen tissues.
  7. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour.
  8. World Health Organization Performance Status of 0 to 1.
  9. Women of childbearing age should take appropriate contraceptive measures from screening to 3 months after stopping the study treatment and should not breastfeed. Before starting the administration, the pregnancy test was negative.
  10. Male patients should be willing to use barrier contraception from screening to stopping study treatment for 3 months.(i.e., condoms).
  11. For inclusion in study, patient must provide a written informed consent.
  12. ≤10 weeks between surgery and randomization.

Exclusion Criteria:

* Any patient who meets any of the following exclusion criteria will not qualify for entry into the study:

  1. Treatment with any of the following:

     1. Pre-operative or post-operative or planned radiation therapy for the current lung cancer
     2. Pre-operative (neo-adjuvant) platinum based or other chemotherapy
     3. Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time
     4. Any other anti-tumor treatment for lung cancer(Including proprietary Chinese patent medicine with anti-tumor effects and anti-tumor immunotherapy, etc.)
     5. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
     6. Treatment with an investigational drug within five half-lives of the compound or any of its related material.
     7. Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug..
  2. Patients who have had only segmentectomies or wedge resections
  3. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for \> 5 years following the end of treatment.
  4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
  5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
  6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of Almonertinib.
  7. Any of the following cardiac criteria:

     1. Mean resting corrected QT interval (QTc) \> 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
     2. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \> 250 ms).
     3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
  8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  9. Inadequate bone marrow reserve or organ function.
  10. History of hypersensitivity to any active or inactive ingredient of Almonertinib, or to drugs with a similar chemical structure or class to Almonertinib.
  11. Patients who are allergic to pemetrexed or any other ingredients in the preparation, cisplatin or other platinum-containing compounds.
  12. Patients with contraindications of pemetrexed and cisplatin.
  13. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
  14. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
  15. Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Secondary outcomes:
measure: Disease free survival (DFS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall Survival (OS)
timeFrame: Start of study drug to Survival Endpoint through study completion, an average of 5 years, assessed up to 100 months
measure: Patient health-related quality of life and symptoms (HRQoL) by SF-36v2 Health Survey
timeFrame: From date of randomization until treatment completion or discontinuation, assessed up to 100 months
Other outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: From date of randomization until 28 days after treatment completion
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Science
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chendu
country: China
facility: Sichuan Cancer Hospital
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
city: Fuzhou
country: China
facility: Fujian Medical University Consonancy Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School Of Medicine
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Nanchang
country: China
facility: JiangXi Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
city: Ningbo
country: China
facility: Ningbo Medical Center Li Huili Hospital
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: ShangHai Chest Hospital ShangHai JiaoTong University
city: Shanghai
country: China
facility: ShangHai Pulmonary Hospital
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center
city: Shijiazhuang
country: China
facility: Hebei Cancer Hospital
city: Sichuan
country: China
facility: West China Hospital，Sichuan University
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Taiyuan
country: China
facility: Thoracic Surgery Department Of The ShanXi Provincial Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Chest Hospital
city: Weifang
country: China
facility: Weifang People's Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Wuhan Union Hospital Of China
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Ürümqi
country: China
facility: Affiliated Tumor Hospital of Xinjiang Medical University
Study officials:
References: