Concurrent Chemoradiotherapy Combination With Anlotinib for Limited-stage Small Cell Lung Cancer

An Exploratory Clinical Study to Investigate Concurrent Chemoradiotherapy Combination With Anlotinib for Limited-stage Small Cell Lung Cancer

The purpose of this study is to evaluate the tolerability and toxicity of different dose of anlotinib combination with concurrent chemoradiotherapy in the treatment of limited-stage SCLC patients.

Study Overview

Detailed Description

Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β c-Kit and MET. The purpose of this study is to determine the maximum tolerated dose of anlotinib when combination with concurrent chemoradiotherapy. From low dose group up to high dose group, each one had 3 patients at least. Primary group received anlotinib 8mg. The dose of anlotinib would increase gradually until MTD.

Study Type

Interventional

Enrollment (Anticipated)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Recruiting
        • Tianjin Medical University Cancer Institute and Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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. Patients voluntarily participate in this study, signed informed consent.
  2. Patients aged between 18 -75 years; According to the eighth edition of AJCC and the standard of the VALG two-stage staging method, the patient is confirmed by histology or cytology as limited-stage SCLC (stage I-III, any T, any N, M0) and cannot be operated on.
  3. Patients with ECOG PS Scoring: 0~1 point
  4. Patients with concurrent chemoradiotherapy must comply with relevant regulations.
  5. PCI is given according to the judgment of the investigator.
  6. Patients with normal organ function, the following criteria are met: (1) blood routine examination criteria (without blood transfusion in 14 days) : a) hemoglobin (HB) ≥90g/L; b) absolute neutrophil count (ANC) ≥1.5×10e9/L; c) platelet (PLT) ≥80×10e9/L; (2) biochemical tests meet the following criteria: a) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); b) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; c) serum creatinine (Cr) ≤1.5 ULN or creatinine clearance (CCr) ≥60mL/min.
  7. For women of child-bearing age, the pregnancy test results (serum or urine) within 1 week before enrolment must be negative. They will take appropriate methods for contraception during the study until the 6 months post the last administration of study drug. For men (previous surgical sterilization accepted), will take appropriate methods for contraception during the study until the 6 months post the last administration of study drug.

Exclusion Criteria:

  1. Small cell and non-small cell mixed lung cancer
  2. Extensive stage small cell lung cancer
  3. Central lung tumors that imaging shows tumor lesions invade local large blood vessels; or with significant pulmonary cavum or necrotizing
  4. Less than 4 weeks from the last clinical trial or participating in other clinical studies.
  5. History:

1) Brain metastasis or spinal cord compression 2) Other active malignancies that require simultaneous treatment. 3) History of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or history of organ transplantation.

4) History of mental drug abuse and cannot be cured or have mental disorders 6. Patients with any severe and/or uncontrolled disease, including:

  1. blood pressure control is not ideal (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg);
  2. Significant cardiac disease as defined as: grade I or greater myocardial infarction, unstable arrhythmia (including corrected QT interval (QTc ) period between male or greater 450 ms, female or greater 470 ms); New York Heart Association (NYHA) grade II or greater heart dysfunction , or Echocardiography reveal left ventricular ejection fraction (LVEF) less than 50%
  3. Decompensated diabetes or other remedies for high-dose glucocorticoid therapy.
  4. Exacerbation of chronic obstructive pulmonary disease (COPD) or other serious respiratory diseases that require hospitalization
  5. Active or uncontrollable serious infection (≥CTC AE Level 2 infection);
  6. Uncontrolled pleural effusion, pericardial effusion and abdominal effusion requiring repeated drainage.
  7. Urine routine test protein≥++, and confirmed 24 hours urine protein>1.0 g; 7. Imaging shows that the tumor has been violated around important vascular or the researchers determine the tumor is likely to invade important blood vessels caused by fatal bleeding during the follow-up.

8. Patients who received a major surgical treatment or severe trauma, the effects of surgery or trauma have been eliminated in less than 2 weeks before being enrolled 9. Patients with clinically significant hemoptysis occurred within 3 months prior to enrollment (greater than 1/2 teaspoon of bright red blood). History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage, hemorrhagic acne, bleeding gastric ulcer, occult blood test ≥ ++, or vasculitis, etc.) 10. Patients who have arterial/venous thromboembolism events within 6 months before being enrolled, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.

11. Coagulation disfunction(INR>1.5 or PT>upper limit of normal(ULN)+4s or activated partial thromboplastin time (APTT) >1.5 upper limit of normal (ULN)), hemorrhagic tendency or receiving the therapy of thrombolysis or anticoagulation.

12. At the discretion of the investigator, the patient may have other factors that may cause the study to be terminated midway.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Concurrent chemoradiotherapy plus anlotinib
Concurrent chemoradiotherapy plus anlotinib for 4-6 cycles This study will include a sequential evaluation of 3 subjects per dose group. Low-dose groups: anlotinib 8mg per day with concurrent chemoradiotherapy. Middle-dose groups: anlotinib 10mg per day with concurrent chemoradiotherapy. High-dose groups: anlotinib 12mg per day with concurrent chemoradiotherapy.

Anlotinib: for cycle 1-6. P.O; QD; from days 1 to 14 in a 21-day cycle. 8mg in low-dose groups (3 subjects). 10mg in middle-dose groups (3 subjects). 12mg in high-dose groups (3 subjects).

Chemotherapy:

For cycle 1/4/5/6. Etoposide 100mg/m2, d1-3, q3w; Cisplatin 25mg/m2 d1-3, q3w. For cycle 2/3. Etoposide 50mg/m2, d1-3, q4w; Cisplatin 25mg/m2 d1-3, q4w.

Radiotherapy:

For cycle 2/3.Thoracic radiotherapy dose will be 2.0Gy per day, given 5 days a week, to cumulative dose of 60~66Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.
Time Frame: From enrollment to completion of study. Estimated about 18months
Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria
From enrollment to completion of study. Estimated about 18months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS(Overall Survival)
Time Frame: From enrollment until death (up to 24 months)
OS was defined as time from date of enrollment to date of death due to any cause.
From enrollment until death (up to 24 months)
PFS(Progress free survival)
Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
The PFS time is defined as time from enrollment to locoregional or systemic
each 42 days up to intolerance the toxicity or PD (up to 24 months)
ORR(Objective Response Rate)
Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.
each 42 days up to intolerance the toxicity or PD (up to 24 months)
DCR(Disease Control Rate)
Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease).
each 42 days up to intolerance the toxicity or PD (up to 24 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 7, 2021

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

July 1, 2023

Study Registration Dates

First Submitted

May 7, 2021

First Submitted That Met QC Criteria

May 7, 2021

First Posted (Actual)

May 11, 2021

Study Record Updates

Last Update Posted (Actual)

May 11, 2021

Last Update Submitted That Met QC Criteria

May 7, 2021

Last Verified

May 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individal participant data for all primary and secondary outcome measures will be made available.

IPD Sharing Time Frame

Data will be available within 6 months of study completion

IPD Sharing Access Criteria

Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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