Chemotherapy Plus Immunotherapy Combined With SBRT as Neoadjuvant Therapy for Patients With Resectable NSCLC

NCT06718309 | Recruiting Phase 2

• 1 other identifier: HZCH-2024-003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, patients with EGFR/ALK wild-type, resectable locally advanced NSCLC are expected to receive 1 cycle of chemoimmunotherapy as neoadjuvant therapy, followed by SBRT to the primary lung lesion, and chemoimmunotherapy for 2 cycles. Surgical treatment will be given within 4-6 weeks after the last cycle of chemoimmunotherapy, then immunotherapy maintenance for 1 year.

Conditions

Non-Small Cell Lung Cancer

Keywords

NSCLC; locally advanced; resectable; SBRT; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR)

  Pathological complete response for surgical patients

  Assessed up to 24 weeks

Secondary Outcomes (4)

• Major pathologic response (MPR)

  Assessed up to 24 weeks

• 1-year event-free survival (1 year EFS)

  Assessed up to 100 months

• The R0 resection rate

  Assessed up to 24 weeks

• Incidence of treatment-related adverse events

  assessed up to 100 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Treatment group

Drug: Chemotherapy; Drug: Immunotherapy; Procedure: Radical resection of lung cancer; Radiation: SBRT

Interventions

Chemotherapy DRUG

Patients with squamous cell carcinoma can choose paclitaxel + cisplatin/carboplatin and patients with nonsquamous cell carcinoma can choose pemetrexed + cisplatin/carboplatin. The chemotherapy treatment lasts 3 cycles.

Treatment group

Immunotherapy DRUG

Investigators choose PD-1 or PD-L1 according to drug indication and the immunotherapy lasts 3 cycles preoperatively and 1 year after surgery.

Treatment group

Radical resection of lung cancer PROCEDURE

Radical resection of lung cancer with lymph node dissection

Treatment group

SBRT RADIATION

SBRT for primary lung lesion 8Gy\*3F after first cycle of chemoimmunotherapy

Treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or pathologically confirmed, newly diagnosed non-small cell lung cancer patients;
• Age ≥18 years;
• (Eastern Cooperative Oncology Group, ECOG) (Performance Status, PS) score 0-1;
• According to the 8th-9th edition of (American Joint Committee on Cancer, AJCC) (stage II-IIIA, for stage IIIB included T3-4N2, T4 only included tumor \> 7cm);
• Puncture or biopsy samples were tested EGFR/ALK negative;
• Surgically or potentially resectable after discussion by multidisciplinary team (MDT);
• Who has not received systemic antitumor therapy and has not received chest radiotherapy;
• Evaluable lesions in the lung or mediastinum;
• The organ function level should meet the following criteria one week before enrollment: 1) Bone marrow function: hemoglobin ≥80g/L, white blood cell count ≥4.0\*10\^9/L or neutrophil count ≥1.5\*10\^9/L, platelet count ≥100\*10\^9/L; 2) Liver: total serum bilirubin level ≤1.5 times the normal upper limit, when serum total bilirubin level \> 1.5 times the normal upper limit, direct bilirubin level ≤ normal upper limit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the normal upper limit; 3) Kidney: blood creatinine level \< 1.5 times the normal upper limit or creatinine clearance ≥50ml/min, urea nitrogen ≤200mg/L; Serum albumin ≥30g/L;
• Male/female of childbearing age agrees to use contraception during the trial period (surgical ligation or oral contraceptives/IUDs + condom contraception);
• Sign informed consent.

You may not qualify if:

• Patients with severe dysfunctions of the heart, lungs and other organs who are not suitable for surgery;
• Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granuloma), etc;
• Other malignancies within 5 years (excluding non-melanoma skin cancer and cervical cancer);
• Patient with active infection, heart failure, heart attack, unstable angina pectoris or unstable arrhythmia within the last 6 months;
• Congenital or acquired immunodeficiency disorders include human immunodeficiency virus (HIV) or a history of organ transplantation or allogeneic stem cell transplantation;
• Patients treated with other immunological agents, chemotherapy agents, other drugs in clinical trials and long-term cortisol therapy were excluded;
• Patients who are allergic or contraindicated to PD-1 inhibitors.

Sponsors & Collaborators

• First People's Hospital of Hangzhou: lead

Study Sites (1)

Department of Thoracic Oncology, Hangzhou Cancer Hospital

Hangzhou, Zhejiang, 310002, China

RECRUITING

Related Publications (5)

• Zhang JT, Liu SY, Gao W, Liu SM, Yan HH, Ji L, Chen Y, Gong Y, Lu HL, Lin JT, Yin K, Jiang BY, Nie Q, Liao RQ, Dong S, Guan Y, Dai P, Zhang XC, Yang JJ, Tu HY, Xia X, Yi X, Zhou Q, Zhong WZ, Yang XN, Wu YL. Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non-Small Cell Lung Cancer. Cancer Discov. 2022 Jul 6;12(7):1690-1701. doi: 10.1158/2159-8290.CD-21-1486.

  PMID: 35543554 RESULT

• Xia L, Mei J, Kang R, Deng S, Chen Y, Yang Y, Feng G, Deng Y, Gan F, Lin Y, Pu Q, Ma L, Lin F, Yuan Y, Hu Y, Guo C, Liao H, Liu C, Zhu Y, Wang W, Liu Z, Xu Y, Li K, Li C, Li Q, He J, Chen W, Zhang X, Kou Y, Wang Y, Wu Z, Che G, Chen L, Liu L. Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1). Clin Cancer Res. 2022 Aug 2;28(15):3308-3317. doi: 10.1158/1078-0432.CCR-21-3044.

  PMID: 34844976 RESULT

• Qiu B, Guo W, Zhang F, Lv F, Ji Y, Peng Y, Chen X, Bao H, Xu Y, Shao Y, Tan F, Xue Q, Gao S, He J. Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC. Nat Commun. 2021 Nov 19;12(1):6770. doi: 10.1038/s41467-021-27022-z.

  PMID: 34799585 RESULT

• Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol. 2023 Aug;20(8):543-557. doi: 10.1038/s41571-023-00782-x. Epub 2023 Jun 6.

  PMID: 37280366 RESULT

• Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. doi: 10.1056/NEJMoa2302983. Epub 2023 Jun 3.

  PMID: 37272513 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy

Study Officials

• Lucheng Zhu, MD

  Hangzhou Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Tang

CONTACT

86-15068763710; Beebee24@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this study, patients with surgically resectable locally advanced non-small cell lung cancer (stage II-IIIA and part of stage IIIB) (EGFR/ALK wild-type for adenocarcinoma patients) are enrolled. Eligible patients firstly receive one cycle of chemoimmunotherapy, followed by stereotactic body radiotherapy (SBRT) (8Gy\*3F) to the primary lung lesion and then continued with another two cycles of chemoimmunotherapy. Surgical treatment was performed within 4-6 weeks after the last chemoimmunotherapy. Immunotherapy continues until 1 year after surgery. Minimal residue lesion (MRD) are monitored at 5 timepoints during the treatment period.

Study Record Dates

• First Submitted: November 24, 2024
• First Posted: December 5, 2024
• Study Start: April 24, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029
• Last Updated: December 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)