Clinical Trials /

First-line Chemotherapy Followed by Toripalimab Combined With Anlotinib for Maintenance in ES-SCLC

NCT04363255

Description:

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).

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First-line Chemotherapy Followed by Toripalimab Combined With Anlotinib for Maintenance in ES-SCLC
  • 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

Clinical Trial IDs

  • ORG STUDY ID: LDQ-202004
  • NCT ID: NCT04363255

Conditions

  • Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
Etoposide InjectionEtoposideMaintenance group
Carboplatin InjectionCarboplatinMaintenance group
Cisplatin injectionCisplatinMaintenance group
ToripalimabJS001Maintenance group
Anlotinib hydrochlorideAnlotinibMaintenance group

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Maintenance groupExperimentalAfter 4-6 cycles of EP/EC chemotherapy regiment, maintenance therapy with toripalimab and anlotinib was followed and continued until disease progression.
  • Etoposide Injection
  • Carboplatin Injection
  • Cisplatin injection
  • Toripalimab
  • Anlotinib hydrochloride

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:PFS

Secondary Outcome Measures

Measure:Adverse event (AE)
Time Frame:Duration of time from the start of treatment to the end of study, assessed up to 3 years
Safety Issue:
Description:The acute and chronic AE profiles associated with the study regimen using CTCAE v5.0
Measure:Objective response rate (ORR)
Time Frame:Duration of time from the start of treatment to the end of study, assessed up to 3 years
Safety Issue:
Description:ORR was the sum percentage of partial response (PR) and stable disease (SD) according to RECIST v1.1
Measure:Disease control rate (DCR)
Time Frame:Duration of time from the start of treatment to the end of study, assessed up to 3 years
Safety Issue:
Description:DCR was the sum percentage of complete response (CR), partial response (PR) and stable disease (SD) according to RECIST v1.1
Measure: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
Safety Issue:
Description:DoR

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Taizhou Hospital

Last Updated

April 26, 2020