Clinical trial NCT04201756: Neoadjuvant Afatinib Therapy for Potentially Resectable Stage III EGFR Mutation-Positive Lung Adenocarcinoma
Official title: Neoadjuvant Afatinib Therapy for Potentially Resectable Stage III EGFR Mutation-Positive Lung Adenocarcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Adenocarcinoma Stage III
EGFR Gene Mutation
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2019-12-17
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In general, for patients with stage I or II disease, surgery provides the best chance for cure.EGFR tyrosine kinase inhibitors(TKIs)are standard first-line treatment for EGFR-mutant advanced NSCLC.Afatinib was a 2nd-generation EGFR TKI that covalently bound and irreversibly blocked signaling through activated EGFR, human epidermal growth factor receptor 2 (HER2), and ErbB4 receptors, and the FDA has approved afatinib for first-line treatment of patients with metastatic NSCLC who have sensitizing EGFR mutations.The treatment of stage III NSCLC remains a matter of debate. Current multimodality treatment options for stage III included definitive chemoradiation, surgery followed by adjuvant therapy,or neoadjuvant therapy followed by surgical resection.Previous studies have revealed that adjuvant EGFR-TKI could significantly prolong disease free surivival, and have less toxicity than adjuvant chemotherapy for early resectable EGFR mutation positive NSCLC patients.EMERGING-CTONG1103 regarding neoadjuvant erlotinib vs chemotherapy (Gemcitabine plus cisplatin) for stage III NSCLC reveal that erlotinib has improved ORR (54%), major pathological response, operation rate, R0 resection and lymph node downstaging, and progression-free survival (PFS).A phase II trial (ASCENT) of neoadjuvant afatinib for stage III EGFR-mutation NSCLC concludes that afatinib yields the highest ORR (75%) up to now and verifies the feasibility of neoadjuvant EGFR TKIs for stage III NSCLC. However, no more studies are available so far to confirm the efficacy and safety of neoadjuvant afatinib in the treatment of resectable stage III EGFR mutation-positive NSCLC, and there is a lack of studies based on the Chinese population. Given that the neoadjuvant therapy has delayed the operation time and there is a potential risk of cancer progression, more data are needed to perform evaluation.


Eligibility criteria: Inclusion Criteria:

* Lung adenocarcinoma patient with EGFR sensitive mutation as confirmed by needle biopsy;
* At stage III (TNM Staging, Version 8) as identified by chest CT, PET-CT or/and EBUS;
* No systemic metastasis (confirmed by head MRI, whole body bone scan, PET-CT, liver and adrenal CT, etc.);
* With the feasiblility or potential feasibility to receive radical surgery (radical lung lobectomy+systematic lymph node dissection);
* Good lung function that could tolerate surgical treatment;
* Aged \>= 18 years;
* At least one measurable tumor foci (the longest diameter measured by CT shall be \> 10 mm);
* Other major organs shall function well (liver, kidney, blood system, etc.):
* ECOG PS score shall be 0-1;
* The child-bearing female must undergo pregnancy test within 7 days before starting the treatment and the result shall be negative. Reliable contraceptive measures, such as intrauterine device, contraceptive pill and condom, shall be adopted during the trial and within 30 days after completion of the trial. The child-bearing male shall use condom for contraception during the trial and within 30 days after completion of the trial;
* The patient shall sign the Informed Consent Form.

Exclusion Criteria:

* The patient has undergone any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment, etc.;
* The patient suffered from other cancers besides NSCLC (except cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor \[including Ta and Tis\]) within 5 years before the trial;
* The patient suffers from any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina pectoris, angina pectoris that starts to attack within the last 3 months, congestive heart failure \[≥ Grade II specified by New York Heart Association (NYHA)\], cardiac infarction (6 months before enrollment), severe arrhythmia and liver, kidney or metabolic diseases that requires drug treatment;
* The patient is a carrier of active hepatitis B, hepatitis C or HIV;
* The patient suffers from severe or new-onset gastrointestinal diseases with diarrhea as the main symptom;
* The patient is receiving the P glycoprotein inhibitor therapy;
* The patient has had or is currently suffering from cardiovascular malformation;
* The patient has had or is currently suffering from interstitial lung disease;
* The patient had undergone other major systemic operations or suffered from severe trauma within 3 months before the trial;
* The patient is allergic to afatinib or its any excipients;
* The patient suffers from nervous system diseases or mental diseases and cannot keep compliance with the trial;
* The patient has any malabsorption condition;
* The female patient is in pregnancy or lactation period;
* There are any conditions under which the investigator considers the patient is not suitable to be enrolled.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 11 weeks
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: up to 60 months
measure: Disease free survival (DFS)
timeFrame: up to 100 months
measure: Overall survival (OS)
timeFrame: up to 60 months
measure: Progression-free survival (PFS)
timeFrame: up to 60 months
measure: R0 resection
timeFrame: 9 weeks
measure: Pathological downstaging rate
timeFrame: 11 weeks
measure: Treatment-related adverse events
timeFrame: 12 weeks
measure: Health related quality of life (HRQol)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Shang'ai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: