Neoadjuvant Afatinib Combination With Chemotherapy for Stage Ⅱa-Ⅲb NSCLC With EGFR Activating Mutation
NCT ID: NCT04470076
Last Updated: 2020-07-14
Study Results
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Basic Information
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UNKNOWN
PHASE2
30 participants
INTERVENTIONAL
2020-07-10
2023-07-30
Brief Summary
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Detailed Description
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The investigators propose that neoadjuvant EGFR-TKI combination with chemotherapy for stage Ⅱa-Ⅲb NSCLC with EGFR activating mutation might have better pathological response and disease-free survival (DFS) than chemotherapy alone, and maximize benefit early in a patient's treatment course. At the same time, dynamic 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) was used to evaluate the standardized uptake value (SUV) and uptake rate constant (Ki) changes of lesions before and after treatment, so as to accurately and quantitatively monitor the tumor response of different therapy.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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neoadjuvant afatinib combination with chemotherapy
Neoadjuvant treatment (chemotherapy+afatinib) will start within 1-3 days from enrollment/randomisation. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment (including dynamic 18F-FDG PET/CT) will be done. Patients must leave the study if there is evidence of progression. Patients with stable disease or partial response may be considered for surgery.
Surgery: Surgery must be done within the 3rd-4th week (+7 days) from day 21 cycle 3 of neoadjuvant treatment (day 42-49 after day 1 of cycle 3) Adjuvant treatment (afatinib): Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the first week (+ 7 days) from surgery and up to 2 years.
Surgical treatment
The patients who respond to neoadjuvant treatment (CR+PR) and the patients who do not respond to therapy but could still undergo surgery (SD and PD) will receive radical lung resection 3-4 weeks later after neoadjuvant.
Adjuvant treatment:afatinib
The CR, PR and SD patients who have been treated surgically will take afatinib at a dosage of 30mg per day for 2 year.
Neoadjuvant treatment: Afatinib, pemetrexed, gemcitabine, cisplatin, carboplatin
① Eligible patients with non-squamous cell lung cancer will receive pemetrexed 500mg/m2, IV on day 1 and cisplatin 75mg/m2 or carboplatin area under curve (AUC) =5, on day 1 of a 3-week schedule for 3 cycles.
② Eligible patients with squamous cell lung cancer will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 or carboplatin AUC =5 on day 1 of a 3-week schedule for 3 cycles .
③Patient will take afatinib at dosage of 30mg per day 48 hours after chemotherapy and will stop 24 hours before next cycle of chemotherapy.
Interventions
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Surgical treatment
The patients who respond to neoadjuvant treatment (CR+PR) and the patients who do not respond to therapy but could still undergo surgery (SD and PD) will receive radical lung resection 3-4 weeks later after neoadjuvant.
Adjuvant treatment:afatinib
The CR, PR and SD patients who have been treated surgically will take afatinib at a dosage of 30mg per day for 2 year.
Neoadjuvant treatment: Afatinib, pemetrexed, gemcitabine, cisplatin, carboplatin
① Eligible patients with non-squamous cell lung cancer will receive pemetrexed 500mg/m2, IV on day 1 and cisplatin 75mg/m2 or carboplatin area under curve (AUC) =5, on day 1 of a 3-week schedule for 3 cycles.
② Eligible patients with squamous cell lung cancer will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 or carboplatin AUC =5 on day 1 of a 3-week schedule for 3 cycles .
③Patient will take afatinib at dosage of 30mg per day 48 hours after chemotherapy and will stop 24 hours before next cycle of chemotherapy.
Eligibility Criteria
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Inclusion Criteria
* Computed tomography (CT) or PET-CT within the last 30 days showing radiographic stage Ⅱa to Ⅲb lung cancer (mediastinal staging biopsy is allowed but not required) by the American Joint Committee on Cancer (AJCC) 8th edition
* Deemed surgically resectable by a senior thoracic surgeon
* Age≥18 years, and ≤75 years
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator
* Adequate tissue specimens for correlative biomarker analysis. The patient should be willing to provide tissue from a newly obtained biopsy of a tumor lesion and surgical resected tumor lesion.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE version (v)5.0 grade 1
* Be willing and able to provide written informed consent for the trial
* Absolute neutrophil count (ANC) \>= 1500 cells/ microlitre(uL) (within 10 days prior to the start of trial treatment)
* Platelets \>= 100 000 cells/uL (within 10 days prior to the start of trial treatment)
* Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks) (within 10 days prior to the start of trial treatment)
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance, glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) \>= 30 mL/min for patients with creatinine levels \> 1.5 x institutional ULN (within 10 days prior to the start of trial treatment)
* Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (within 10 days prior to the start of trial treatment)
* Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver metastases) (within 10 days prior to the start of trial treatment)
* International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of trial treatment)
* Activated partial thromboplastin time (aPTT)/PTT =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of trial treatment)
* Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Male and female patients of childbearing potential must be willing to use an adequate method of contraception as outlined, for the course of the trial through 120 days after the last dose of trial drug
* Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
Exclusion Criteria
* Hormone-replacement therapy or oral contraceptives
* Herbal therapy \> 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)
* Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and prostate-specific antigen (PSA) ≤ 10 mg/mL, etc.)
* Patients who are receiving any other investigational agents concurrently.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to afatinib, cisplatin, carboplatin, pemetrexed or gemcitabine.
* Patients with active hepatitis B or C infections or a history of HIV infection.
* Patients with past or resolved hepatitis B infection, defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive for the antibody test to detect antibodies to hepatitis B core antigen (anti-HBc) are eligible.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection including tuberculosis (TB), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
* Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
* Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
* Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
* Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study
* Pregnant women
* History of interstitial lung disease or pneumonitis of any cause
* Is ineligible for an operation based on medical or oncologic contraindications to surgery
* Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment
* Note: Patients who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
18 Years
75 Years
ALL
No
Sponsors
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Fifth Affiliated Hospital, Sun Yat-Sen University
OTHER
Responsible Party
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Central Contacts
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Other Identifiers
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ZDWY.XXWK002
Identifier Type: -
Identifier Source: org_study_id
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