Clinical Trials /

Neoadjuvant Afatinib Therapy for Resectable Stage III EGFR Mutation-Positive Lung Adenocarcinoma

NCT04201756

Description:

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.

Related Conditions:
  • Lung Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Afatinib Therapy for Resectable Stage III EGFR Mutation-Positive Lung Adenocarcinoma
  • Official Title: Neoadjuvant Afatinib Therapy for Resectable Stage III EGFR Mutation-Positive Lung Adenocarcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial

Clinical Trial IDs

  • ORG STUDY ID: 1200.0328
  • NCT ID: NCT04201756

Conditions

  • Lung Adenocarcinoma Stage III
  • EGFR Gene Mutation

Interventions

DrugSynonymsArms
AfatinibAfatinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AfatinibExperimental
  • Afatinib

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 to receive radical surgery (radical lung lobectomy+systematic
             lymph node dissection);

          -  Good lung function that could tolerate surgical treatment;

          -  Aged 18-75 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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:11 weeks
Safety Issue:
Description:ORR is defined as the proportion of patients who have completed the 8-week treatment with afatinib before operation and have achieved CR or PR as confirmed by CT evaluation after 3 weeks in all patients.

Secondary Outcome Measures

Measure:Disease free survival (DFS)
Time Frame:up to 60 months
Safety Issue:
Description:From date of randomization until the date of first disease release or date of death from any cause, whichever came first, assessed up to 60 months
Measure:Overall survival (OS)
Time Frame:up to 100 months
Safety Issue:
Description:From date of randomization until the date of date of death from any cause, whichever came first, assessed up to 100 months.
Measure:Progression-free survival (PFS)
Time Frame:up to 60 months
Safety Issue:
Description:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Measure:R0 resection
Time Frame:9 weeks
Safety Issue:
Description:It is defined as the proportion of patients with negative surgical margin and no residual found under microscope after resection in all patients who have completed the treatment.
Measure:Pathological downstaging rate
Time Frame:11 weeks
Safety Issue:
Description:It is defined as the proportion of patients who have completed the 8-week treatment with afatinib before operation and have achieved a T stage downing of the tumor as confirmed by CT evaluation after 3 weeks in all patients who have completed the treatment.
Measure:Treatment-related adverse events
Time Frame:12 weeks
Safety Issue:
Description:It refers to the number of adverse events related to afatinib monotherapy or platinum-based chemotherapy as evaluated according to CTCAE v4.0.
Measure:Health related quality of life (HRQol)
Time Frame:12 weeks
Safety Issue:
Description:The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-C30 & LC13, Version 3). EORTC's QLQ-C30 & LC13 (V3.0) is a core scale for lung cancer patients, with a total of 43 items. Among them, Item 29 and 30 are divided into seven grades, which are assigned with 1 to 7 scores according to the answer options. The other items are divided into 4 grades: Not at All, A Little, Quite a Bit, and Very Much, assigned with 1 to 4 scores respectively. The higher score, the worse quality.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shanghai Pulmonary Hospital, Shanghai, China

Last Updated

December 14, 2019