Potentially Resectable Stage II/IIIa NSCLC
Conditions
Keywords
NSCLC, Durvalumab, medi4736
Brief summary
Combination treatment of Durvalumab with chemoradiotherapy is ongoing for head/neck cancer, renal cell carcinoma, melanoma, and non-small cell lung cancer (NCT02318771) and pancreatic cancer (NCT02305186).Combining Durvalumab with neoadjuvant chemoradiotherapy is a promising strategy to improve clinical outcome in stage III lung cancer. Using serial biopsied and surgically resected fresh tissue through the novel/high-throughput RNA sequencing technologies, we want to identify the change immune signature in tumor microenvironment of NSCLC patients after Durvalumab treatment. With hypothesis that PD-1 inhibitor as a component of neoadjuvant chemoradiotherapy followed by surgery could increase complete pathologic response rate and disease free survival, and overall survival, we suggest adding Durvalumab to neoadjuvant chemoradiation in stage II/III resectable NSCLC. And with immune marker study using FACS, whole exome sequencing, or RNAsequencing, we can find the potential predictive biomarker for anti-PD-L1 blockade. And in this study, we can get "whole" surgical specimen not biopsy sample after Durvalumab treatment so the analysis for immune marker, tumor microenvironment, and various tumor infiltrating immune cells and their changes will be available.
Interventions
DRUGdurvalumab
Neo-adjuvant chemoradiation period The treatment consisted of paclitaxel, carboplatin, duvalumab and radiation. The radiation treatment comprises 45Gy (total 25Fr) and that will be about 5 weeks. Intensity modulated RT (IMRT) or 3D CRT (three-dimensional conformal radiotherapy) will be allowed. Surgery Chest CT and/or PET CT with appropriate other diagnostic method (ex. Bronchoscopy) will be performed before surgery and type of surgery Follow-up period There is every 4 month visit with chest CT and abdominal CT is done at 1,2,5 post-op year. Other diagnostic method can be performed if indicated.
Sponsors
Yonsei University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For inclusion in the study subjects must fulfill all of the following criteria: 1. Histologically confirmed NSCLC 2. Clinical stage III (including N2 stage and potential candidate for resection) 3. Written informed consent and any locally-required authorization (IRB) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 4. Age \> 20 years at time of study entry 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Adequate normal organ and marrow function as defined below: * Haemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1,500μL * Platelet count ≥ 100,000μL * Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). \<This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\> * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN * Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: * Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) --Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) 6. Life expectancy of 6 months 8. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥50 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. 9\. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion criteria
Subjects should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of patients who experience G3 or more treatment-related adverse events (TRAEs) based on CTCAE 5.0 | for 5 year | To evaluate safety and tolerability of neoadjuvant chemoradiation therapy in combination with durvalumab in NSCLC |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) | from date of randomization until the date of first documented progression, assessed up to 5 years |
| DFS (disease free survival) | from date of randomization until the date of first documented progression, assessed up to 5 years |
| OS (overall survival) | from date of randomization until the date of first documented progression, assessed up to 5 years |
| clinical and pathologic down staging rate | from date of randomization until the date of first documented progression, assessed up to 5 years |
Countries
South Korea
Contacts
CONTACTByoung Chul Cho, MD
Outcome results
None listed