Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer
Study Details
Study Description
Brief Summary
This is a randomized, open label study designed to evaluate the efficacy and safety of neoadjuvant PD-1 antibody plus chemotherapy followed by surgery in resectable stage IIIA-N2 non-small cell lung cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is an open-label, randomised, two-arm, phase II, multi-centre clinical trial. The proposed study will evaluate the efficacy and safety of preoperative administration PD-1 antibody plus chemotherapy in patients resectable stage IIIA-N2 NSCLC. Data obtained in this study will provide valuable information for planning further phase III clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Neoadjuvant PD-1 antibody puls chemotherapy Neoadjuvant treatment (PD-1 antibody+carboplatin+pemetrexed or nab-paclitaxel ) will start within 1-3 days from enrollment. 3 cycles will be administered at 21-day (+/- 3 days) intervals (QW3) prior to surgery. Before surgery a tumor assessment will be done. Patients with stable disease or partial response may be considered for surgery. Surgery: Surgery must be done within the 4rd-6th week from day 1 cycle 3 of neoadjuvant treatment (day 29-43 after day 1 of cycle 3) Adjuvant treatment: Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 2rd to 8th week from surgery. Three cycles of combinded adjuvant treatment (PD-1 antibody+carboplatin+pemetrexed or nab-paclitaxel ) will be administered. Thirteen cycles of PD-1 antibody will start within day 21-24 days from day 1 of adjuvant cycle 2. |
Drug: Carboplatin
(IV, Q3W)
Drug: Pemetrexed or Nab-paclitaxel
Pemetrexed (Nonsquamous NSCLC) or Nab-paclitaxel (Squamous NSCLC) (IV, Q3W)
Drug: PD-1 antibody
(IV, Q3W)
|
| Active Comparator: Neoadjuvant chemotherapy Neoadjuvant treatment (carboplatin+pemetrexed or nab-paclitaxel ) 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 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 4rd-6th week from day 1 cycle 3 of neoadjuvant treatment (day 29-43 after day 1 of cycle 3). Adjuvant treatment: Patients that are R0 confirmed by surgical pathology evaluation will receive the first adjuvant administration within the 2rd to 8th week from surgery. Three cycles of adjuvant treatment (carboplatin+pemetrexed or nab-paclitaxel ) will be administered. |
Drug: Carboplatin
(IV, Q3W)
Drug: Pemetrexed or Nab-paclitaxel
Pemetrexed (Nonsquamous NSCLC) or Nab-paclitaxel (Squamous NSCLC) (IV, Q3W)
|
Outcome Measures
Primary Outcome Measures
- PFS at 24 months [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.]
The PFS is defined as the time from diagnosis to relapse, progression or death, whichever occurred first.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent provided.
-
Males or females aged ≥18 years.
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Pathologically diagnosed of non-small cell lung cancer.
-
Diagnosed as stage IIIA- N2.The diagnosis standard of N2 is as below: Pts with resectable stage IIIA-N2 NSCLC confirmed by mediastinoscopy or EBUS and PET/CT.
-
Tumor should be considered resectable before study entry by a multidisciplinary team.
-
ECOG (Performance status) 0-1.
-
Screening laboratory values must meet the following criteria and should be obtained within 7 days prior to randomization.
- Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 x×109/L iii. Hemoglobin > 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min v. AST/ALT ≤ 3 x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or >40% predicted value viii. INR/APTT within normal limits.
-
Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before randomization.
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All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs.
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Patient capable of proper therapeutic compliance and accessible for correct follow-up.
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Measurable or evaluable disease (according to RECIST 1.1 criteria).
Exclusion Criteria:
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All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.
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Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
-
Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team.
-
Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy.
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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 complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
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Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information.
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Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
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Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
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Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
-
Patients with history of allergy to study drug components excipients.
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Women who are pregnant or in the period of breastfeeding.
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Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Hospital of Lanzhou University | Lanzhou | Gansu | China | |
| 2 | The Second Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | |
| 3 | Changzheng Hospital | Shanghai | Shanghai | China | 200000 |
| 4 | Changhai Hospital | Shanghai | Shanghai | China | 200092 |
| 5 | Shanghai General Hospital | Shanghai | Shanghai | China | 200092 |
| 6 | Shanghai Pulmonary Hospital | Shanghai | Shanghai | China | 200092 |
| 7 | Shuguang Hospital | Shanghai | Shanghai | China | 200092 |
| 8 | Zhejiang Cancer Hospita | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- Shanghai Pulmonary Hospital, Shanghai, China
Investigators
- Principal Investigator: Chang Chen, MD, PhD, Shanghai Pulmonary Hospital, School of Medicine, Tongji University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NALAN-01