Neoadjuvant Afatinib Combination With Chemotherapy for Stage Ⅱa-Ⅲb NSCLC With EGFR Activating Mutation

NCT04470076 | Unknown Phase 2 DMC

• 1 other identifier: ZDWY.XXWK002
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The recommended adjuvant therapy for stage Ⅱa-Ⅲb Non-small cell lung cancer (NSCLC) were perioperative chemotherapy. The adjuvant or neoadjuvant chemotherapy for early stage lung cancer improved about 5% 5-year survival. As for advanced NSCLC with epidermal growth factor receptor (EGFR) activating mutation, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combination with chemotherapy had improved progression-free survival (PFS) compared with EGFR-TKI alone. We propose this trial of Neoadjuvant Afatinib Combination With Chemotherapy for Stage Ⅱa-Ⅲb NSCLC With EGFR Activating Mutation, which would 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

Non Small Cell Lung Cancer; Surgery; EGFR Activating Mutation; Chemotherapy; EGFR TKI

Keywords

neoadjuvant therapy; dynamic 18F-FDG PET/CT

Outcome Measures

Primary Outcomes (2)

• Major pathological response

  10% or less residual viable tumor cells

  up to 12 weeks; analysis of surgical resected tumor samples after neoadjuvant therapy

• Objective response rate

  Image assessment of tumor response according to RECIST 1.1 criteria

  up to 12 weeks; after neoadjuvant therapy

Secondary Outcomes (6)

• Progression free survival

  Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan (ECT) every 12 months for up to 3 years

• Overall survival

  up to 100 months

• R0 resection

  up to 12 weeks; analysis of surgical resected tumor samples

• Treatment related adverse events

  12 weeks

• standardized uptake value (SUV) changes

  up to 12 weeks; before and after neoadjuvant therapy

Study Arms (1)

neoadjuvant afatinib combination with chemotherapy

EXPERIMENTAL

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.

Drug: Neoadjuvant treatment: Afatinib, pemetrexed, gemcitabine, cisplatin, carboplatin; Procedure: Surgical treatment; Drug: Adjuvant treatment:afatinib

Interventions

Neoadjuvant treatment: Afatinib, pemetrexed, gemcitabine, cisplatin, carboplatin DRUG

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.

neoadjuvant afatinib combination with chemotherapy

Surgical treatment PROCEDURE

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.

neoadjuvant afatinib combination with chemotherapy

Adjuvant treatment:afatinib DRUG

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 afatinib combination with chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed NSCLC, performed on a biopsy that occurred within the last 60 days
• 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)

You may not qualify if:

• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 years prior to initiation of study treatment; however, the following are allowed:
• 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

Sponsors & Collaborators

• Fifth Affiliated Hospital, Sun Yat-Sen University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Gemcitabine; Cisplatin; Carboplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Central Study Contacts

QingDong Cao, MD

CONTACT

+8607562528824; cqd8866@163.com

Hua Cheng, PHD

CONTACT

+8607562528825; chenghuagz@hotmail.com

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: July 3, 2020
• First Posted: July 14, 2020
• Study Start: July 10, 2020
• Primary Completion: December 30, 2021
• Study Completion: July 30, 2023
• Last Updated: July 14, 2020

Record last verified: 2020-06