Non Small Cell Lung Cancer
Conditions
Brief summary
Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant chemotherapy and immunotherapy with Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months.
Detailed description
Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant chemotherapy and immunotherapy with Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months. Three cycles of neoadjuvant chemotherapy in combination with nivolumab will be administered. After completion of neoadjuvant therapy (3 cycles) and before surgery, a tumor assessment will be done. Patients have to leave the study if there is evidence of progression. Patients with in-stable disease or partial response may be considered for surgery. The report imaging response vs pathological response rate will be evaluated. Patients eligible for the trial are those with a histological diagnosis or cytologically proven operable and resectable non-small-cell lung cancer. The total number of patients to be included will be 46 from 23 participating sites in Spain. Accrual period of 1.5 years or until the inclusion of the last patient necessary to achieve the sample set in the protocol of 46 patients. After that all patients will be treated for 1 year with adjuvant immunotherapy and they will be followed during 3 years after adjuvant treatment.
Interventions
DRUGNivolumab 360 mg
Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months
Paclitaxel 200mg/m2 IV Q3W
Carboplatin AUC 6 IV Q3W
Sponsors
Spanish Lung Cancer Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subjects eligible for the study are those with histologically- or cytologically- documented NSCLC who present stage IIIA disease. Locally advanced patients who present stage IIIA by the previous version can be included if are considered potencially resectable. In case of N2 disease suspicion, pathological assessment by EBUS, mediastinoscopy or thoracotomy has to be carried out for N2 confirmation. 2. Tumor should be considered resectable before study entry 3. Performance Status of 0 or 1 4. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration/inclusion i. WBC ≥ 2000/μL ii. Neutrophils ≥ 1500/μL iii. Platelets ≥ 100 x103/μL iv. Hemoglobin \> 9.0 g/dL v. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): a. Female CrCl = (140 - age in years) x weight in kg x 0.85 1\. 72 x serum creatinine in mg/dL b. Male CrCl = (140 - age in years) x weight in kg x 1.00 1. 72 x serum creatinine in mg/dL vi. AST/ALT ≤ 3 x ULN vii. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) viii. INR/APTT within normal limits 5\. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters 6\. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and nacional guidelines, including the Declaration of Helsinki prior to any trial-related intervention. 7\. Patients aged \> 18 years 8\. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. 9\. Women must not be breastfeeding 10\. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.
Exclusion criteria
1. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene. 2. Patients with active, known or suspected autoimmune disease. 3. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. 4. Patients with a history of interstitial lung disease cannot be included if they have sympthomatic ILD (Grade 3-4) 5. Patients with other active malignancy requiring concurrent intervention 6. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a 7. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study 8. Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, 9. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) 10. Patients with known history of testing positive for human immunodeficiency virus (HIV) 11. Patients with history of allergy to study drug components excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | at 24 months from the first dose of neoadjuvant treatment | The progression free survival is the percentage of the patients without disease progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | at 3 years from the first dose of neoadjuvant treatment | Percentage of patients are still alive |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months
Nivolumab 360 mg: Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months
Paclitaxel 200mg/m2: Paclitaxel 200mg/m2 IV Q3W
Carboplatin AUC 6: Carboplatin AUC 6 IV Q3W | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 8.9 |
| Cigarette Smoking History Current smoker | 21 Participants |
| Cigarette Smoking History Former smoker (≥ 1 year) | 25 Participants |
| Cigarette Smoking History Never smoker | 0 Participants |
| ECOG Performance Status Scale ECOG 0 | 25 Participants |
| ECOG Performance Status Scale ECOG 1 | 21 Participants |
| ECOG Performance Status Scale ECOG 2 | 0 Participants |
| ECOG Performance Status Scale ECOG 3 | 0 Participants |
| ECOG Performance Status Scale ECOG 4 | 0 Participants |
| ECOG Performance Status Scale ECOG 5 | 0 Participants |
| Histology Adenocarcinoma | 26 Participants |
| Histology NOS/Undifferenciated | 4 Participants |
| Histology Squamous | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Region of Enrollment Spain | 46 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 34 Participants |
| Tumor node, metastasis staging classification T1N1M0 | 1 Participants |
| Tumor node, metastasis staging classification T1N2M0 | 15 Participants |
| Tumor node, metastasis staging classification T2N1M0 | 1 Participants |
| Tumor node, metastasis staging classification T2N2M0 | 6 Participants |
| Tumor node, metastasis staging classification T3N1M0 | 1 Participants |
| Tumor node, metastasis staging classification T3N2M0 | 13 Participants |
| Tumor node, metastasis staging classification T4N0M0 | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 46 |
| other Total, other adverse events | 43 / 46 |
| serious Total, serious adverse events | 3 / 46 |
Outcome results
Primary
Progression Free Survival
The progression free survival is the percentage of the patients without disease progression
Time frame: at 24 months from the first dose of neoadjuvant treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Progression Free Survival | 77.1 percentage of participants |
Secondary
Overall Survival
Percentage of patients are still alive
Time frame: at 3 years from the first dose of neoadjuvant treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Overall Survival | 89.9 percentage of participants |