A Study of Concurrent Chemoradiation With Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

NCT ID: NCT04636762

Last Updated: 2022-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-05-01

Brief Summary

Etoposide-cisplatin/ -carboplatin in combination with PD-L1 inhibitor for 4 cycles followed by maintenance therapy with PD-L1 inhibitor is currently the world-wide first-line treatment for extensive-stage small cell lung cancer. When 4 cycles of EC/EP chemotherapy combined with PD-L1 inhibitor are effective, guidelines recommend additional thoracic radiotherapy.

In our study, the investigators bring radiotherapy forward, which means that after 2 cycles of EC/EP chemotherapy plus Atezolizumab, participants with response（PR/CR/SD）will receive concurrent radiotherapy and 2 cycles of EC/EP chemotherapy plus Atezolizumab, then maintenance therapy with Atezolizumab （Q3W）.

The purpose of this study is to explore the safety and efficacy of Atezolizumab combined with concurrent chemoradiotherapy in untreated participants with extensive-stage small cell lung cancer.

Detailed Description

participants receive EC/EP chemotherapy combined with Atezolizumab for 2 cycles, and the efficacy will be evaluated. If the efficacy evaluation is SD/PR/CR, concurrent chemoradiotherapy comined with EC/EP(2 cycles) +Atezolizumab will be initiated. After concurrent chemoradiotherapy +Atezolizumab, Atezolizumab was maintained until PD or intolerance or for at most 2 years.

participants with brain metastases will receive radiotherapy for brain metastases during the first 2 cycles of chemotherapy.

Conditions

Extensive-stage Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (etoposide, cisplatin, carboplatin, radiation, Atezolizumab)

Participants receive EC/EP chemotherapy combined with Atezolizumab（ PD-L1 inhibitor）for 2 cycles, and the efficacy is evaluated 2 weeks after the treatment. If the efficacy evaluation is SD/PR/CR, concurrent chemoradiotherapy with EC/EP(2 cycles) + Atezolizumab） will be initiated. After concurrent chemoradiotherapy+ Atezolizumab, Atezolizumab was maintained until PD or intolerance or for at most 2 years. Participants with brain metastases will receive radiotherapy forbrain metastases during the first 2 cycles of chemotherapy.

Group Type: EXPERIMENTAL

Radiation Therapy

Intervention Type: PROCEDURE

Thoracic Radiation Dose: 3Gy, QD, total dose: 30-45Gy; Particpants with brain metastases：metastatic lesions≤3:whole brain radiotherapy with local simultaneous PGTV:50Gy/10F；metastatic lesions\>3:whole brain radiotherapy PTV:30Gy/10F.

Interventions

Radiation Therapy

Thoracic Radiation Dose: 3Gy, QD, total dose: 30-45Gy; Particpants with brain metastases：metastatic lesions≤3:whole brain radiotherapy with local simultaneous PGTV:50Gy/10F；metastatic lesions\>3:whole brain radiotherapy PTV:30Gy/10F.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1.Histologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system) 2.Must sign a written informed consent form prior to any study specific procedures 3. No prior treatment for ES-SCLC 4.Measurable disease, as defined by RECIST v1.1 5.Can tolerate radiotherapy, no contraindication of radiotherapy 6.Weight≥40kg 7.Life expectancy>12 weeks 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1. 9.Systemic immunosuppressive doses of corticosteroids (prednisone>10 mg/d or equivalent) was discontinued at least 2 weeks before registration for protocol therapy.

10. Be willing to provide 20 tissue sections(4-6 micron thickness) from a newly obtained core or excisional biopsy of a tumor lesion, for biomarker exploration; newly-obtained is defined as a specimen obtained within 3 months before initiation of treatment on day 1; newly-obtained samples must be core needle biopsy, excision, or incision 11.Must have adequate organ function defined by the following laboratory results:

1. Absolute neutrophil count (ANC) ≥ 1.5×109/L, Platelets≥ 100×109/L, Hemoglobin≥90g/L

2. Serum creatinine ≤ 1.5 upper limit of normal (ULN) OR calculated creatinine clearance≥60 mL/min(using Cock-Gault formula)

3. Total bilirubin ≤1.5 ULN or for total bilirubin level ≥1.5 ULN, direct bilirubin is within normal limits; AST (SGOT) and ALT (SGPT)≤2.5 ULN.

5. International normalized ratio(INR) or prothrombin time(PT), activated partial thromboplastin time (APTT)≤1.5 ULN, exception: In subjects receiving anticoagulant therapy, as long as PT or APTT is within the recommended use of anticoagulants

6. Baseline ECG showed no prolonged PR interval or atrioventricular block. 12.Women of child-bearing potential should agree that contraception (such as intrauterine devices(LUD), birth control pills or condoms) must be used during the course of the study through 6 months after the last dose of study medication, and women of childbearing potential should have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication and must be a non-lactation participant; the male participants agree to use contraception during the study period and for 6 months after the end of the study period.

Exclusion Criteria

1. Hypersensitivity to Atezolizumab

2. Carcinomatous meningitis.

3. History of active Bacillus tuberculosis (TB)

4. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

5. HIV positive or with Acquired Immune Deficiency Syndrome

6. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy

7. History of, or any evidence of active, non-infectious pneumonitis

8. Immunosuppressive drug was used 2 weeks prior to the first study drug treatment, excluding topical glucocorticoid, systematic glucocorticoid not exceeding 10 mg/d of prednisone or equivalent dose of other glucocorticoid

9. Received a live vaccine within 30 days of planned start of study therapy

10. Received a prior anti-cancer monoclonal antibody (mAb) within 3 months prior to study day 1

11. Has taken Chinese herbal medicine for anti-cancer purpose in the past 2 weeks

12. Known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (HCV) (e.g., HCV ribonucleic acid [RNA] [qualitative] is detected)

13. Active infection requiring systemic therapy

14. Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

15. Bleeding tendency, such as active peptic ulcer, or treated with anticoagulants or vitamin K antagonists, such as Warfarin, Heparin, or their analogues

16. Any severe and/or uncontrolled disease, such as: (1) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months prior to randomization, severe uncontrolled arrhythmia; poor blood pressure control (SBP>140 mmHg, DBP>90 mmHg) ; (2)active or uncontrolled severe infection; (3)liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis; (4) poor control of diabetes (FBG>10mmol/l) ; (5) urine routine suggested urinary protein ≥ + + and 24-hour urinary protein quantitation >1.0 g; (6) history of psychotropic substance abuse and could not be cured or had mental disorder

17. Prisoner who is imprisoned or forcibly detained for reasons other than mental or physical (e.g. infectious) disease

18. Can not tolerate venipuncture

19. Pregnant or lactating women

20. Other conditions that researchers consider unsuitable for participation -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hunan Cancer Hospital

OTHER

Sponsor Role: collaborator

Second Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

xianling liu

director of the oncology department of the Second Xiangya Hospital of Central South University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hunan cancer hospital

Changsha, Hunan, China

the second Xiangya hospital

Changsha, Hunan, China

Countries

China

References

Liu C, Zeng L, Deng C, Jiang W, Wang Y, Zhou Y, Liu L, Wang S, Zhou C, Qiu Z, Zeng F, Wu F, Weng J, Liu X, Yang N, Ma F. Hypofractionated radiotherapy with immunochemotherapy for extensive-stage small-cell lung cancer. Front Immunol. 2023 Jun 7;14:1175960. doi: 10.3389/fimmu.2023.1175960. eCollection 2023.

Reference Type: DERIVED

PMID: 37350968 (View on PubMed)

Other Identifiers

SCLC-LXL001

Identifier Type: -

Identifier Source: org_study_id