Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

Official title:

Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer: A Randomized Phase II Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04422392
• Other study ID #: NALAN-01
• Status: Terminated
• Phase: Phase 2
• Start date: July 13, 2020
• Est. completion date: September 30, 2022

Study information

• Verified date: August 2023
• Source: Shanghai Pulmonary Hospital, Shanghai, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 93
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent provided.

• Males or females aged =18 years.

• 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.

i. 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.

• 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.

• Patient capable of proper therapeutic compliance and accessible for correct follow-up.

• Measurable or evaluable disease (according to RECIST 1.1 criteria).

Exclusion Criteria:

• All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Women who are pregnant or in the period of breastfeeding.

• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Carboplatin
(IV, Q3W)
• Pemetrexed or Nab-paclitaxel
Pemetrexed (Nonsquamous NSCLC) or Nab-paclitaxel (Squamous NSCLC) (IV, Q3W)
• PD-1 antibody
(IV, Q3W)

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospita	Hangzhou	Zhejiang
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Changhai Hospital	Shanghai	Shanghai
China	Changzheng Hospital	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	Shuguang Hospital	Shanghai	Shanghai
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Pulmonary Hospital, Shanghai, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS at 24 months	The PFS is defined as the time from diagnosis to relapse, progression or death, whichever occurred first.	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.