Concurrent Chemoradiotherapy Combined With Toripalimab and Surufatinib in the Treatment of Limited-Stage Small Cell Lung Cancer

NCT ID: NCT06719700

Last Updated: 2024-12-16

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

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-30

Study Completion Date

2028-11-29

Brief Summary

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Based on the preclinical rationale for combining surufatinib with immunotherapy, and the clinical efficacy observed with surufatinib in extensive-stage small cell lung cancer (ES-SCLC), the investigators hypothesize that incorporating surufatinib into the ADRIATIC regimen could further enhance survival in LS-SCLC. To evaluate this approach, the investigators plan to conduct a single-arm Phase II study to explore the safety and efficacy of concurrent chemoradiotherapy combined with toripalimab and surufatinib in treating LS-SCLC.

Detailed Description

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This single-arm Phase II study aims to explore the safety and efficacy of concurrent chemoradiotherapy combined with toripalimab and surufatinib in treating LS-SCLC. In this single-arm, Phase II study, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the consolidation therapy.

Conditions

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Toripalimab Surufatinib Chemoradiotherapy Limited-stage Small Cell Lung Cancer (LS-SCLC)

Keywords

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Toripalimab Surufatinib Chemoradiotherapy Limited-stage small cell lung cancer (LS-SCLC) Immunotherapy consolidation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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The study group

In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.

Group Type EXPERIMENTAL

Chemotherapy

Intervention Type DRUG

Etoposide combined with cisplatin or carboplatin, administered every three weeks for a total of four cycles.

Immunotherapy

Intervention Type DRUG

Toripalimab was administered concurrently with chemotherapy, every three weeks for four cycles.

Angio-immuno kinase inhibitor

Intervention Type DRUG

Oral surufatinib 200 mg once daily (q.d.), given on days 1-14 of each chemotherapy cycle.

radiotherapy

Intervention Type RADIATION

Thoracic radiotherapy will begin no later than the start of the third chemotherapy cycle.

Prophylactic Cranial Irradiation

Intervention Type RADIATION

PCI is recommended after the completion of chemoradiotherapy.

Consolidation Therapy with Toripalimab and Surufatinib

Intervention Type DRUG

Patients achieving complete response (CR), partial response (PR), or stable disease (SD) following chemoradiotherapy will receive consolidation therapy. Toripalimab: 240 mg intravenously on day 1, every three weeks. Surufatinib: 200 mg orally on days 1-14, every three weeks.

Interventions

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Chemotherapy

Etoposide combined with cisplatin or carboplatin, administered every three weeks for a total of four cycles.

Intervention Type DRUG

Immunotherapy

Toripalimab was administered concurrently with chemotherapy, every three weeks for four cycles.

Intervention Type DRUG

Angio-immuno kinase inhibitor

Oral surufatinib 200 mg once daily (q.d.), given on days 1-14 of each chemotherapy cycle.

Intervention Type DRUG

radiotherapy

Thoracic radiotherapy will begin no later than the start of the third chemotherapy cycle.

Intervention Type RADIATION

Prophylactic Cranial Irradiation

PCI is recommended after the completion of chemoradiotherapy.

Intervention Type RADIATION

Consolidation Therapy with Toripalimab and Surufatinib

Patients achieving complete response (CR), partial response (PR), or stable disease (SD) following chemoradiotherapy will receive consolidation therapy. Toripalimab: 240 mg intravenously on day 1, every three weeks. Surufatinib: 200 mg orally on days 1-14, every three weeks.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Informed Consent: An informed consent form, signed and dated, must be provided before any steps in the study are performed.
* Age: Males or females aged 18 to 75 years.
* Diagnosis: Histologically or cytologically confirmed small cell lung cancer (SCLC).
* Stage: Stage I-III (AJCC/UICC 8th edition TNM staging), where all lesions can be included in a single radical radiotherapy plan (i.e., limited-stage disease). Stage I-II must be inoperable.
* Life Expectancy: ≥12 weeks.
* Performance Status (PS): WHO PS score of 0 or 1.
* Postmenopausal women or those with a negative urine or serum pregnancy test (HCG sensitivity ≥25 IU/L or equivalent) within 7 days before starting study treatment.
* Female participants must not be breastfeeding.
* Women of childbearing potential (WOCBP) must agree to use contraception during study treatment and for 3 months after the last dose of study drug (i.e., 30 days for an ovulation cycle plus approximately 5 half-lives of the investigational drug).
* Male participants engaging in sexual activity with WOCBP must agree to use contraception during study treatment and for 5 months after the last dose of study drug (i.e., 90 days for sperm regeneration cycle plus approximately 5 half-lives of the investigational drug).
* Males with azoospermia do not need to follow contraception requirements.
* WOCBP who are not sexually active do not need to follow contraception requirements but must still undergo pregnancy testing as outlined.
* Organ and Bone Marrow Function:

Pulmonary Function: FEV1 ≥800 mL. Absolute neutrophil count ≥1.5 × 10⁹/L. Platelet count ≥100 × 10⁹/L. Hemoglobin ≥9.0 g/dL. Renal Function: Calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula.

Serum bilirubin ≤1.5 × upper limit of normal (ULN). AST and ALT ≤2.5 × ULN.

Exclusion Criteria

* Participation in Another Clinical Trial: Simultaneous participation in another clinical trial, unless it is an observational (non-interventional) study.
* Mixed Histology: Histological subtype of mixed small cell and non-small cell lung cancer (SCLC).
* Extensive-Stage SCLC: Diagnosis of extensive-stage SCLC.
* Malignant Effusions: Pathologically confirmed malignant pleural effusion or pericardial effusion.
* Hemoptysis: Central cavitary SCLC with hemoptysis (hemoptysis volume \>50 ml/day).
* Immunosuppressive Treatment: Use of immunosuppressive drugs within 28 days prior to the first dose of toripalimab. Physiological doses of intranasal corticosteroids and systemic corticosteroids ≤10 mg daily of prednisone (or equivalent) are exceptions. Steroids used to manage chemoradiotherapy-related toxicities are allowed.
* Previous Anti-PD-1/PD-L1 Therapy: Prior use of any anti-PD-1 or anti-PD-L1 antibodies.
* Major Surgery: Underwent major surgery (excluding vascular access) within 4 weeks before study entry.
* Autoimmune Disease History: History of autoimmune diseases within the last 2 years, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis.
* Primary Immunodeficiency: History of primary immunodeficiency.
* Organ Transplant History: History of organ transplantation requiring immunosuppressive treatment.
* QT Interval Prolongation: QTc interval (corrected by Bazett's formula) \>470 ms, calculated from three ECG measurements.
* Uncontrolled Comorbidities: Uncontrolled comorbid conditions, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, active bleeding disorders, chronic hepatitis C, HIV infection, HBsAg-positive patients with DNA \>500 IU/ml, or any psychiatric or social conditions that may interfere with study requirements or the patient's ability to provide informed consent.
* Tuberculosis History: Known history of tuberculosis.
* Live Vaccination: Received a live attenuated vaccine within 30 days prior to study initiation.
* Previous Primary Malignancy: History of another primary malignancy within 5 years prior to study entry, except for adequately treated basal or squamous cell carcinoma of the skin, in situ cervical cancer, ductal carcinoma in situ of the breast, or localized prostate cancer.
* Pregnancy and Breastfeeding: Pregnant or breastfeeding women, or men and women of reproductive potential who are not using effective contraception.
* Interference with Study Assessment: Any condition that may interfere with the evaluation of toripalimab's efficacy or safety.
* Investigator's Discretion: Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Hui Liu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hui Liu, Professor

Role: PRINCIPAL_INVESTIGATOR

Sun yat-sen universtiy cancer center

Locations

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Sun yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Bo Qiu, Professor

Role: CONTACT

Phone: +862087343031

Email: [email protected]

Hui Liu, Professor

Role: CONTACT

Phone: +862087343031

Email: [email protected]

Facility Contacts

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Hui Liu, MD

Role: primary

References

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Zhang Y, Huang Y, Yang Y, Zhao Y, Zhou T, Chen G, Zhao S, Zhou H, Ma Y, Hong S, Zhao H, Zhang L, Fang W. Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/II trial. Signal Transduct Target Ther. 2024 Sep 27;9(1):255. doi: 10.1038/s41392-024-01974-2.

Reference Type BACKGROUND
PMID: 39327433 (View on PubMed)

Li, X. et al. Enhanced anticancer efficacy via ROS-dependent ferroptosis: Synergy between surufatinib and cisplatin in small cell lung cancer. Cancer Res 84(6_Supplement), 2122 (2024)

Reference Type BACKGROUND

Zhou, J. et al. Preclinical evaluation of sulfatinib, a novel angio-immuno kinase inhibitor targeting VEGFR, FGFR-1 and CSF-1R kinases. AACR 77, abs 4187 (2017)

Reference Type BACKGROUND

David R. Spigel et al., ADRIATIC: Durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). JCO 42, LBA5-LBA5(2024).

Reference Type BACKGROUND

Senan S, Okamoto I, Lee GW, Chen Y, Niho S, Mak G, Yao W, Shire N, Jiang H, Cho BC. Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clin Lung Cancer. 2020 Mar;21(2):e84-e88. doi: 10.1016/j.cllc.2019.12.006. Epub 2019 Dec 28.

Reference Type BACKGROUND
PMID: 31948903 (View on PubMed)

Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. doi: 10.1200/JCO.2002.12.071.

Reference Type BACKGROUND
PMID: 12118018 (View on PubMed)

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

Reference Type BACKGROUND
PMID: 30207593 (View on PubMed)

Other Identifiers

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GASTO-10123

Identifier Type: -

Identifier Source: org_study_id