Anlotinib Plus Etoposide and Carboplatin as First-line Treatment for Extensive-stage Small Cell Lung Cancer

Anlotinib Plus Etoposide and Carboplatin as First-line Treatment for Extensive-stage Small Cell Lung Cancer: A Single Arm Phase II Trial

This is a phase II, open-label, single center study, aiming to investigate safety and efficacy of etoposide and carboplatin (administered intravenously) in combination with anlotinib (administered orally) in treatment-naive advanced NSCLC.

Study Overview

• Status: Unknown
• Conditions: SCLC; Anlotinib
• Intervention / Treatment: Drug: Anlotinib hydrochloride; Drug: Etoposide; Drug: Carboplatin

Detailed Description

Lung cancer can be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), of which SCLC accounts for about 15%-20%.Because of the high degree of malignancy of SCLC, patients often lose the opportunity of surgical treatment due to metastasis at the time of admission. Traditional cytotoxic drugs can improve the prognosis of patients and life treatment, but the survival benefit is very limited.

Vascular targeted therapy is an important treatment strategy for metastatic lung cancer.Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor that has significant inhibitory activity against angiogenesis related kinases such as VEGFR1/2/3, FGFR1/2/3, and other tumor related kinases such as PDGFR /, C-Kit, Ret, etc. (e.g., Met, FGFR1/2/3). An exploratory phase II study explored the efficacy of third-line single-drug therapy for ED-SCLC and found significant improvement in prognosis.

Based on the above status and research results, the purpose of this study was to explore the efficacy and safety of anlotinib hydrochloride combined with etoposide/carboplatin in first-line treatment of extensive small-cell lung cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Baohui Han; Phone Number: 8618930858216 8618930858216; Email: 18930858216@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with extensive stage SCLC confirmed by histology or cytology and are confirmed to have at least one measurable lesion according to RECIST 1.1.
2. Without active brain metastasis
3. Previously treated with ICIs with progressive disease.
4. Age ≥18 years and ≤75 years;
5. ECOG PS score: 0 to 1
6. The main organs function is normal, that is, the following criteria met: good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment]; biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 times ULN; if the subject is receiving anticoagulant treatment, PT should be within the prescribed range of use of anticoagulant drugs;
7. Women of child-bearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and within 6 months after the study; non-breast-feeding patients whose serum or urinary pregnancy test should be negative; male patients should agree to take contraceptive measures during the study and within 6 months after the study.
8. Patients are voluntarily enrolled into the study, sign the informed consent form and have good compliance.

Exclusion Criteria:

1. Subjects with active CNS metastases are excluded.
2. Non-small cell lung cancer.
3. With obvious hemorrhage symptom
4. Patients with many factors affecting oral medication, such as dysphagia, gastrointestinal resection, chronic diarrhea and intestinal obstruction.
5. Combined with other tumors at the time of initial diagnosis.
6. Patients who have previously participated in other clinical trials and have not yet terminated the trial.
7. Patients who have acute infection that difficult to control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anlotinib plus etoposide and carboplatin; Etoposide and carboplatin plus anlotinib for 4 cycles and anlotinib as maintenance therapy	Drug: Anlotinib hydrochloride; anlotinib 10 mg/day orally (from days 1 to 14 in a 21-day cycle); Other Names: anlotinib; Drug: Etoposide; 100mg/m2 iv on days 1-3 every 21 days for 4 cycles; Other Names: VP-16; Drug: Carboplatin; AUC 5 iv on day 1 every 21 days for 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Time from enrollment to progression or death	Time from randomization to progression, assessed 9-11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Patients who were assessed as partial response or complete response	6-9 weeks
OS	Time from enrollment to death of any cause	13-15 months
DCR	Patients who were assessed as partial response, complete response or stable disease	6-9 weeks

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Investigators: Study Director: Baohui Han, Shanghai Chest Hospital

Publications and helpful links

General Publications

• Zhang W, Deng P, Kong T, Zhang B, Qian F, Dong Y, Chen Y, Chen L, Liu D, Zhang Y, Yang H, Han B. Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2). Lung Cancer. 2022 Nov;173:43-48. doi: 10.1016/j.lungcan.2022.09.003. Epub 2022 Sep 8.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 24, 2020
• Last Update Submitted That Met QC Criteria: December 22, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: SCLC; Anlotinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide
• Other Study ID Numbers: KS2039

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No