A Trial of Anlotinib Combined With Concurrent Chemoradiotherapy in Patients With Unresectable Stage III Non-small Cell Lung Cancer

NCT04958993 | Terminated Phase 1

• 1 other identifier: SDZLEC2019-069-03
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Progress free survival (PFS) for phase Ⅱ

  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.

  up to 30 months

• Maximum Tolerance Dose (MTD) for phaseⅠ

  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

  From enrollment to completion of study. Estimated about 18months

Secondary Outcomes (2)

• 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)

Study Arms (1)

Anlotinib combined with concurrent chemoradiotherapy

EXPERIMENTAL

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)

Drug: Anlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy

Interventions

Anlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy DRUG

radiotherapy (five days a week to accept chest radiotherapy, once per day, every time 1.8-2.0 Gy, total dose 54-66 Gy) AND chemotherapy (Squamous cell carcinoma selective platinum + docetaxel and Adenocarcinoma selective platinum + Pemetrexed) AND Anlotinib Hydrochloride capsule (12mg QD PO d1-14, 21 days per cycle)

Anlotinib combined with concurrent chemoradiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. Patients of childbearing age (including female and female partners of male patients) must take effective birth control measures

You may not qualify if:

• \. 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;
• \. Patients whose tumors have invaded important blood vessels according to imaging findings or whose tumors are likely to invade important blood vessels during the follow-up study according to the judgment of the researchers, resulting in fatal massive hemorrhage;
• \. Patients with any physical signs or history of bleeding, regardless of severity;Patients with any bleeding or bleeding event ≥CTCAE level 3 within 4 weeks prior to enrollment have unhealed wounds, ulcers or fractures;
• \. Occurrence of ARTERIAL/venous thrombotic events, such as cerebrovascular accidents (including temporary ischemic attacks), deep venous thrombosis and pulmonary embolism within 6 months;
• \. Persons with a history of abuse of psychotropic substances and who cannot be cured or have mental disorders;
• \. Pregnant and lactating women;

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• JINGMIN YU, PhD

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the hospital

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: July 12, 2021
• Study Start: November 12, 2020
• Primary Completion: November 20, 2021
• Study Completion: November 22, 2021
• Last Updated: February 25, 2022

Record last verified: 2022-02

Locations

CN (1)