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

NCT ID: NCT06718309

Last Updated: 2024-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-24

Study Completion Date

2029-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Non-Small Cell Lung Cancer

Keywords

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NSCLC locally advanced resectable SBRT immunotherapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment group

Treatment group

Group Type EXPERIMENTAL

Chemotherapy

Intervention Type 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.

Immunotherapy

Intervention Type DRUG

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

Radical resection of lung cancer

Intervention Type PROCEDURE

Radical resection of lung cancer with lymph node dissection

SBRT

Intervention Type RADIATION

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

Interventions

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Chemotherapy

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.

Intervention Type DRUG

Immunotherapy

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

Intervention Type DRUG

Radical resection of lung cancer

Radical resection of lung cancer with lymph node dissection

Intervention Type PROCEDURE

SBRT

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

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

1. Histologically or pathologically confirmed, newly diagnosed non-small cell lung cancer patients;
2. Age ≥18 years;
3. (Eastern Cooperative Oncology Group, ECOG) (Performance Status, PS) score 0-1;
4. 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);
5. Puncture or biopsy samples were tested EGFR/ALK negative;
6. Surgically or potentially resectable after discussion by multidisciplinary team (MDT);
7. Who has not received systemic antitumor therapy and has not received chest radiotherapy;
8. Evaluable lesions in the lung or mediastinum;
9. 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;
10. Male/female of childbearing age agrees to use contraception during the trial period (surgical ligation or oral contraceptives/IUDs + condom contraception);
11. Sign informed consent.

Exclusion Criteria

1. Patients with severe dysfunctions of the heart, lungs and other organs who are not suitable for surgery;
2. 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;
3. Other malignancies within 5 years (excluding non-melanoma skin cancer and cervical cancer);
4. Patient with active infection, heart failure, heart attack, unstable angina pectoris or unstable arrhythmia within the last 6 months;
5. Congenital or acquired immunodeficiency disorders include human immunodeficiency virus (HIV) or a history of organ transplantation or allogeneic stem cell transplantation;
6. Patients treated with other immunological agents, chemotherapy agents, other drugs in clinical trials and long-term cortisol therapy were excluded;
7. Patients who are allergic or contraindicated to PD-1 inhibitors.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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First People's Hospital of Hangzhou

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lucheng Zhu, MD

Role: PRINCIPAL_INVESTIGATOR

Hangzhou Cancer Hospital

Locations

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Department of Thoracic Oncology, Hangzhou Cancer Hospital

Hangzhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yi Tang

Role: CONTACT

Phone: 86-15068763710

Email: [email protected]

Facility Contacts

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Lihui Fang

Role: primary

References

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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.

Reference Type RESULT
PMID: 35543554 (View on PubMed)

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.

Reference Type RESULT
PMID: 34844976 (View on PubMed)

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.

Reference Type RESULT
PMID: 34799585 (View on PubMed)

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.

Reference Type RESULT
PMID: 37280366 (View on PubMed)

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.

Reference Type RESULT
PMID: 37272513 (View on PubMed)

Other Identifiers

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HZCH-2024-003

Identifier Type: -

Identifier Source: org_study_id