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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
Sponsor:
Information provided by (Responsible Party):
Haihua Yang, Taizhou Hospital

Tracking Information
First Submitted Date  ICMJE April 23, 2020
First Posted Date  ICMJE April 27, 2020
Last Update Posted Date April 28, 2020
Estimated Study Start Date  ICMJE May 1, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-line Chemotherapy Followed by Toripalimab Combined With Anlotinib for Maintenance in ES-SCLC
Official Title  ICMJE 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
Brief Summary Our aim in this study was to evaluate the efficacy and safety of etoposide combined with cisplatin or carboplatin (EC/EP) chemotherapy regimens followed by toripalimab combined with anlotinib for maintenance in extensive small cell lung cancer(ES-SCLC).
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Carcinoma
Intervention  ICMJE
  • 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
  • Drug: Toripalimab
    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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Etoposide Injection
  • Drug: Carboplatin Injection
  • Drug: Cisplatin injection
  • Drug: Toripalimab
  • Drug: Anlotinib hydrochloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Patients must sign a specific informed consent form prior to clinical trial; 2. Extensive stage small cell lung cancer confirmed by histology or cytology; 3. Patients did not receive any system treatment before or only received EP/EC chemotherapy (time from the last medication of chemotherapy to the beginning of maintenance treatment must be ≤21 days); 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 5. An estimated survival duration of >5 months from the beginning of chemotherapy; 6. Age no less than 18; 7. A measurable lesion on image; 8. Patients with asymptomatic brain metastases or symptomatic brain metastases which were stable after treatment; 9. Before the first dose of drugs for study, patients should have appropriate organ function and the laboratory results must meet conditions as following: Blood routine examination: neutrophil absolute value (ANC) ≥1.5×109/L, platelet (PLT) ≥100×109/L, hemoglobin content (HGB) ≥9g/dl; Adequate hepatic function: bilirubin ≤1.5×ULN mg/dl, creatinine clearance ≥ 50 ml/min; Adequate hepatic function: Aspartate aminotransferase (AST) /alanine aminotransferase (ALT)> 2.5 × upper limit of normal (ULN) or > 5 × ULN (patients with liver metastasis), alkaline phosphatase (ALP) ≤2.5×ULN or ≤5×ULN (patients with bone metastasis), Total bilirubin (TB) ≤1.5×ULN, albumin (ALB)>30g/dl; Coagulation function: international normalized ratio (INR) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤1.5×ULN; Urine routine: 24-hour urine protein<1g (if urine protein ≥2+, additional 24-hour urine protein is required); Others: serum lipase or amylase ≤1.5×ULN or >1.5×ULN (subjects clinically or radiologically diagnosed with pancreatitis).

Exclusion Criteria:

  • 1. Patients received EP/EC regiment received the last medication ≥21 days before maintenance treatment, or received other systematic anti-tumor treatment for ES-SCLC; 2. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation; 3. Patients received any other experimental drugs or participated in another interventional clinical study within 4 weeks prior to signing the informed consent; 4. Patients received other systemic or local antitumor therapy (including but not limited to the use of other drugs for SCLC maintenance therapy or radiotherapy, but CR/PR subjects are allowed to use prophylactic cranial irradiation (PCI) after induction period treatment); 5. Patients with active and untreated brain metastases or carcinoma meningitis in CT or MRI examination during screening stage; 6. Patients with other malignant tumors within 5 years, except for curable malignant tumors (carcinoma in situ or stage I tumor), such as cervical carcinoma in situ, basal cell or squamous cell skin cancer and so on); 7. Patients received corticosteroids (>10mg/ day methyl prednisolone or equivalent dose) or other immunosuppressants (inhalation or local use of steroids and adrenal replacement treatment were permitted in the absence of an active autoimmune disease) less than 14 days prior to maintenance medications; 8. Patients with chronic or acute active hepatitis B (HBsAg positive and hepatitis B virus (HBV) DNA copy number >ULN), or HCV positive (HCV Ab positive and HCV RNA positive); Hepatitis B patients with previous HBV infection or who have been cured (HBsAg negative, HBcAb positive and HBV DNA copy number < ULN) were allowed to be enrolled; 9. Patients with interstitial lung disease, drug-induced pneumonia, radiation pneumonitis requiring steroid treatment, or active pneumonia with clinical symptoms; or other lung diseases causing moderate or severe lung dysfunction; Active pulmonary tuberculosis or the need for anti-tuberculosis treatment; 10. Patients who were allergy to one of research drugs, or allergy to any one of the immunocheckpoint inhibitors or other platinum; 11. Female patients during pregnant and lactation period, or patients were plan to pregnant; 12. Patients with factors that may cause the study to be forced to terminate halfway according to investigators' judgement, such as poor compliance, other serious diseases requiring combined treatment and so on.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dongqing Lv, MD 13867622009 lvdq@enzemed.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04363255
Other Study ID Numbers  ICMJE LDQ-202004
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: make individual participant data (IPD) available
Responsible Party Haihua Yang, Taizhou Hospital
Study Sponsor  ICMJE Taizhou Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dongqing Lv, MD Enze Hospital affiliated Taizhou hospital of Wenzhou Medical University
PRS Account Taizhou Hospital
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP