A Phase I/II Clinical Study of Anlotinib Hydrochloride Capsule Combined With Concurrent Chemoradiotherapy in the Treatment of Unresectable Stage III Non-small Cell Lung Cancer

Shandong Cancer Hospital and Institute1 site in 1 country7 target enrollmentNovember 12, 2020

ConditionsNon-small Cell Lung Cancer

InterventionsAnlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy

DrugsAnlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy

Overview

Phase: Phase 1
Intervention: Anlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy
Conditions: Non-small Cell Lung Cancer
Sponsor: Shandong Cancer Hospital and Institute
Enrollment: 7
Locations: 1
Primary Endpoint: Progress free survival (PFS) for phase Ⅱ
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase I/II exploratory study to evaluate the efficacy and safety of anlotinib combined with concurrent chemoradiotherapy in the treatment of surgically unresectable stage III non-small cell lung cancer.

Registry

clinicaltrials.gov

Start Date

November 12, 2020

End Date

November 22, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shandong Cancer Hospital and Institute

Responsible Party

Principal Investigator

Jinming Yu

Director of the hospital

Shandong Cancer Hospital and Institute

Eligibility Criteria

Inclusion Criteria

•The patients volunteered to participate in this study and signed the informed consent;
•Locally advanced (IIIA/IIIC) non-small cell lung cancer patients diagnosed by pathology as newly diagnosed unresectable, inoperable or refused surgery (difficult patients should be evaluated by thoracic multidisciplinary assessment for potential enrollment); .
•Ages 18-75, regardless of gender;
•ECOG score: 0-1;
•Expected survival over 3 months;
•Function of major organs within 7 days prior to treatment meets the following criteria:
•A. Standard of blood routine examination (without blood transfusion within 14 days) :
•I. Hemoglobin (HB) ≥100 g/L; II. WBC ≥3.0×109/L; Iii. Platelet (PLT) ≥100×109/L.
•B. Biochemical examination shall meet the following standards:
•I. Total bilirubin (TBIL) ≤1.5 times the upper limit of normal value (ULN); II. AST≤2.5×ULN of alanine aminotransferase (ALT) and aspartate aminotransferase (ASpartate), if accompanied by liver metastasis, ALT and AST≤5×ULN; III. Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance rate (CCr)≥60ml/min; C. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower normal limit (50%); D. Pulmonary function assessment: FEV1≥1.45 l/s.

Exclusion Criteria

•Patients who have previously used anlotinib hydrochloride capsules;
•Small cell lung cancer (including mixed small cell and non-small cell cancers);
•Lung squamous cell carcinoma with empty cavity, or non-small cell lung cancer with hemoptysis (\> 20ml/day);
•Patients with other malignant tumors other than NSCLC within 5 years before the start of treatment in this study (except those with simple surgical resection and disease-free survival for at least 5 consecutive years, cured cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor);
•Systemic antitumor therapy, including cytotoxic therapy, signal transduction inhibitors and immunotherapy, is planned within 4 weeks before enrollment or during the medication period of this study.In addition to thymosin, lentinan and other immunomodulator treatment.
•Unmitigated toxicity due to any previous treatment above CTC AE level 1, excluding hair loss;
•Patients with multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
•Accompanied by pleural effusion or ascites, causing respiratory syndrome (≥CTC AE level 2 dyspnea);
•Patients with any severe and/or uncontrolled disease, including: A) Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg); B) Having grade I or above myocardial ischemia or infarction, arrhythmia (including QTc ≥480ms), and grade 2 or above congestive heart failure (New York Heart Association (NYHA) classification); C) Active or uncontrolled severe infection (≥CTC AE level 2 infection); D) Antiviral treatment for cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis; E) Renal failure requires hemodialysis or peritoneal dialysis; F) A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; G) poor control of diabetes mellitus (FBG) \> 10mmol/L; H) urine routine indicated urinary protein ≥++, and confirmed 24-hour quantitative urinary protein \> 1.0g; I) patients with epileptic seizures requiring treatment; J) Patients with gastric ulcer
•Receive major surgical treatment, open biopsy or significant traumatic injury within 28 days before grouping;

Arms & Interventions

Anlotinib combined with concurrent chemoradiotherapy

Radiotherapy: 1.8-2.0Gy, qd, 54-66Gy, 5 days a week Chemotherapy: squamous cell cancer: paclitaxel + platinum;Adenocarcinoma: pemetrexed + platinum;A cycle of 3W was used, and the appropriate chemotherapy dose was selected by the researcher according to the patient's situation without any restriction on the chemotherapy dose.Pre-induction chemotherapy is allowed. Anlotinib: QD, take 2 weeks and stop for 1 week (radiotherapy 1, 2, 4, 5 weeks)

Intervention: Anlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy

Outcomes

Primary Outcomes

Progress free survival (PFS) for phase Ⅱ

Time Frame: up to 30 months

PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.

Maximum Tolerance Dose (MTD) for phaseⅠ

Time Frame: From enrollment to completion of study. Estimated about 18months

Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 5.0 criteria

Secondary Outcomes

Overall Survival (OS)(From randomization until death (up to 30 months))
Objective Response Rate (ORR)(each 42 days up to intolerance the toxicity or PD (up to30 months))