Clinical trial NCT04728724: Neoadjuvant Immunotherapy for Stage III Non-small Cell Lung Cancer
Official title: Neoadjuvant Sintilimab or Combined With Chemotherapy for Stage III Driven Gene Mutation Negative Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer Stage III
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2021-01-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II, non-randomized, open-label, multi-center study to evaluate the efficacy of neoadjuvant Sintilimab (PD-1 antibody) or combined with chemotherapy as first-line treatment in patients with stage III non-small cell lung cancer (NSCLC).


Eligibility criteria: Inclusion Criteria:

1. The patient shall sign the Informed Consent Form.
2. Aged 18 ≥ years.
3. Histological or cytological diagnosis of NSCLC by needle biopsy, and stage III confirmed by imageological examinations (CT, PET-CT or EBUS).
4. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1.
5. Life expectancy is at least 12 weeks.
6. At least 1 measurable lesion according to RECIST 1.1.
7. With the feasiblility or anticipated feasiblility after neoadjuvant therapy to receive radical surgery;
8. Patients with good function of other main organs (liver, kidney, blood system, etc.):

   * ANC count ≥1.5×10\^9/L, platelet count ≥100×10\^9/L，hemoglobin ≥90 g/L;
   * the international standard ratio of prothrombin time (INR) and prothrombin time (PT) \< 1.5 times of upper limit of normal (ULN);
   * Partial thromboplastin time (APTT) ≤1.5×ULN;
   * Total bilirubin ≤1.5×ULN;
   * Alanine aminotransferase (ALT) aspartate aminotransferase (AST) ≤2.5×ULN, or ALT and AST ≤5×ULN in the patients with liver metastatic tumor.
9. Patients with normal lung function can tolerate surgery;
10. Without systematic metastasis (including M1a, M1b and M1c);
11. Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of Sintilimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.
12. Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of Sintilimab (whichever is later).

Exclusion Criteria:

1. Non-squamous cell carcinoma with EGFR active mutation positive or ALK rearrangement;
2. Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment;
3. Administration of any Chinese medicine against cancer before administration of the drug;
4. Participants with other cancer (excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder epithelial tumor \[including TA and tis\]) within five years before the start of this study;
5. Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (\>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases;
6. With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment;
7. Antibiotics were used to treat the infection for 4 weeks prior to the start of the trial;
8. Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids \>10 mg/ day) or other immunosuppressive agents within 2 weeks prior to first administration. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal hormone replacement therapy with a dose of less than 10 mg/ day of prednisone are permitted;
9. Participants who are allergic to the test drug or any auxiliary materials;
10. Participants with active hepatitis B, hepatitis C or HIV;
11. The vaccine was administered within 4 weeks of the start of the trial;
12. Participants who have undergone major surgery or severe trauma in other systems within 2 months before the start of this trial;
13. Pleural effusion, pericardial effusion or ascites that are not clinically controlled and require pleural puncture or abdominal puncture drainage within 2 weeks before inclusion;
14. The patients have active pia meningioma, uncontrolled or untreated brain metastases;
15. Pregnant or lactating women;
16. Participants suffering from nervous system diseases or mental diseases that cannot cooperate;
17. Participated in another therapeutic clinical study;
18. Other factors that researchers think it is not suitable for enrollment.

Primary outcomes:
measure: Major pathologic response (MPR)
timeFrame: up to 5 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 4 months
measure: Disease-free survival (DFS)
timeFrame: up to 60 months
measure: Progression-free survival (PFS)
timeFrame: up to 60 months
measure: Overall survival (OS)
timeFrame: up to 60 months
measure: Safety: frequency of severe adverse events
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
References: