First-line Chemotherapy Followed by Toripalimab Combined With Anlotinib for Maintenance in ES-SCLC
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|ClinicalTrials.gov Identifier: NCT04363255|
Recruitment Status : Not yet recruiting
First Posted : April 27, 2020
Last Update Posted : April 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|Small Cell Lung Carcinoma||Drug: Etoposide Injection Drug: Carboplatin Injection Drug: Cisplatin injection Drug: Toripalimab Drug: Anlotinib hydrochloride||Phase 2|
Lung cancer is the most leading malignant tumor, among which small cell lung cancer accounts for about 15%. Approximately 65% of new patients were diagnosed with ES-SCLC at the first visit with less than 6 months of median PFS (mPFS) and 8-13 months of median OS (mOS). Platinum combined with etoposide or irinotecan chemotherapy is the first-line standard chemotherapy treatment. Despite high objective response of initial treatment, it is evitable to develop chemotherapy resistance and the effects of follow-up line treatment is dissatisfying. Therefore, combination therapy may be promising and efficient.
Anlotinib, the brand new multi-target protein tyrosine kinase (PTK) blockers, could normalize distribution of blood vessels in the tumor, gather T cells and enhance effect of immune drugs via vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), type Ⅲ tyrosine kinase and others signal pathways, and then inhibit the growth, proliferation and differentiation of lung cancer cells. According to ALTER1202 study, anlotinib played a promising role in local tumor control and effectively prolonged PFS in third line or more for ES-SCLC patients. Meanwhile, immunocheckpoint inhibitors can improve tumor immune microenvironment, relieve VEGF-mediated immunosuppression, reduce Treg activity, promote tumor antigen presenting ability and better infiltrate T cell into the tumor to play an anti-tumor effect. Emerging studies have shown that immunocheckpoint inhibitors, such as Atezolizumab, Pembrolizumab and Nivolumab, can effectively improve ORR, DoR and survival in SCLC patients. In terms of molecular mechanisms, immunocheckpoint inhibitors and vascular targeting drugs complemented and the combination of two drugs has superior efficacy in non-small cell lung cancer (NSCLC), just as it shown in IMpower150 and other studies. However, the role of immunocheckpoint inhibitors in maintenance therapy in SCLC were disappointing in CheckMate451 and a study of pembrolizumab, although it obtained some victories in first line or more for SCLC.
In summary, the investigators proposed that first-line etoposide/platinum-based chemotherapy followed by toripalimab combined with anlotinib for maintenance may prolong chemo-resistance in extensive small cell lung cancer.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of First-line Etoposide/Platinum-based Chemotherapy Followed by Toripalimab Combined With Anlotinib for Maintenance in Extensive Small Cell Lung Cancer: A Single-arm, Multicentral Phase II Study|
|Estimated Study Start Date :||May 1, 2020|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||March 31, 2023|
Experimental: Maintenance group
After 4-6 cycles of EP/EC chemotherapy regiment, maintenance therapy with toripalimab and anlotinib was followed and continued until disease progression.
Drug: Etoposide Injection
Etoposide(100mg/m2, d1-3, q3w) combined with platinum was the first-line chemotherapy in 4-6 cycles, and then JS001 combined with anlotinib as maintenance therapy were followed.
Other Name: Etoposide
Drug: Carboplatin Injection
Carboplatin(AUC 5, d1, q3w) or Cisplatin combined with etoposide was the first-line chemotherapy in 4-6 cycles, and then JS001 combined with anlotinib as maintenance therapy were followed.
Other Name: Carboplatin
Drug: Cisplatin injection
Cisplatin(75mg/m2, d1, q3w) or carboplatin combined with etoposide was the first-line chemotherapy in 4-6 cycles, and then JS001 combined with anlotinib as maintenance therapy were followed.
Other Name: Cisplatin
After 4-6 cycles of chemotherapy, JS001(240mg, d1, q3w) combined with anlotinib were followed and continued until disease progression.
Other Name: JS001
Drug: Anlotinib hydrochloride
After 4-6 cycles of chemotherapy, anlotinib(12mg qd, d1-14, q3w) combined with JS001 were followed and continued until disease progression.
Other Name: Anlotinib
- Progression free survival (PFS) [ Time Frame: Duration of time from the start of chemotherapy to the time of disease progression, assessed up to 3 years ]PFS
- Overall survival (OS) [ Time Frame: Duration of time from the start of chemotherapy to the time of outcome events, assessed up to 3 years ]OS
- Adverse event (AE) [ Time Frame: Duration of time from the start of treatment to the end of study, assessed up to 3 years ]The acute and chronic AE profiles associated with the study regimen using CTCAE v5.0
- Objective response rate (ORR) [ Time Frame: Duration of time from the start of treatment to the end of study, assessed up to 3 years ]ORR was the sum percentage of partial response (PR) and stable disease (SD) according to RECIST v1.1
- Disease control rate (DCR) [ Time Frame: Duration of time from the start of treatment to the end of study, assessed up to 3 years ]DCR was the sum percentage of complete response (CR), partial response (PR) and stable disease (SD) according to RECIST v1.1
- Duration of response (DoR) [ Time Frame: Duration of time from the start of treatment response to the time of disease progression, assessed up to 3 years ]DoR
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04363255
|Contact: Dongqing Lv, MDemail@example.com|
|Enze Hospital, affiliated Taizhou Hospital of Wenzhou Medical University|
|Taizhou, Zhejiang, China|
|Contact: Dongqing Lv, MD 13867622009 firstname.lastname@example.org|
|Principal Investigator: Dongqing Lv, MD|
|Taizhou, Zhejiang, China|
|Contact: Haihua Yang, MD 13819639006 email@example.com|
|Principal Investigator: Haihua Yang, MD|
|Principal Investigator:||Dongqing Lv, MD||Enze Hospital affiliated Taizhou hospital of Wenzhou Medical University|