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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The study group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chemotherapy | Drug | Etoposide combined with cisplatin or carboplatin, administered every three weeks for a total of four cycles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Median progression-free survival (PFS) | The length of time from the start of treatment until disease progression or death from any cause, whichever occurs first. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Median overall survival (OS) | The time from the start of treatment to death from any cause. | 2 years |
| Treatment-related adverse events | The assessment of treatment-related adverse events (AEs), including their type, severity, frequency, and impact on patients. |
| Measure | Description | Time Frame |
|---|---|---|
| Circulating Tumor DNA | The analysis of variations in ctDNA levels during and after treatment, and their correlation with patient outcomes | 2 years |
Inclusion Criteria:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bo Qiu, Professor | Contact | +862087343031 | qiubo@sysucc.org.cn | |
| Hui Liu, Professor | Contact | +862087343031 | liuhui@sysucc.org.cn |
| Name | Affiliation | Role |
|---|---|---|
| Hui Liu, Professor | Sun yat-sen universtiy cancer center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39327433 | Background | 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. | |
| Background | 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) | ||
| 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) | ||
| 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). |
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| Immunotherapy | Drug | Toripalimab was administered concurrently with chemotherapy, every three weeks for four cycles. |
|
| Angio-immuno kinase inhibitor | Drug | Oral surufatinib 200 mg once daily (q.d.), given on days 1-14 of each chemotherapy cycle. |
|
| radiotherapy | Radiation | Thoracic radiotherapy will begin no later than the start of the third chemotherapy cycle. |
|
| Prophylactic Cranial Irradiation | Radiation | PCI is recommended after the completion of chemoradiotherapy. |
|
| Consolidation Therapy with Toripalimab and Surufatinib | 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. |
|
| 1 year after treatment |
| Patient-Reported Outcomes | Patient reported quality of life measured by European organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30) and QLQ-LC13. | 1 year after treatment |
| 31948903 | 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. |
| 12118018 | Background | 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. |
| 30207593 | Background | 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. |
| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| D007167 | Immunotherapy |
| D011878 | Radiotherapy |
| C000656314 | toripalimab |
| C000717729 | surufatinib |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
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