Non-small Cell Lung Cancer
Conditions
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.
Interventions
DRUGAnlotinib hydrochloride capsule Combined With Concurrent Chemoradiotherapy
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)
Sponsors
Shandong Cancer Hospital and Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. The patients volunteered to participate in this study and signed the informed consent; * 2\. 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); . * 3\. Ages 18-75, regardless of gender; * 4\. ECOG score: 0-1; * 5\. Expected survival over 3 months; * 6\. 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. * 7\. Patients of childbearing age (including female and female partners of male patients) must take effective birth control measures
Exclusion criteria
* 1\. Patients who have previously used anlotinib hydrochloride capsules; * 2\. Small cell lung cancer (including mixed small cell and non-small cell cancers); * 3\. Lung squamous cell carcinoma with empty cavity, or non-small cell lung cancer with hemoptysis (\> 20ml/day); * 4\. 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); * 5\. 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. * 6\. Unmitigated toxicity due to any previous treatment above CTC AE level 1, excluding hair loss; * 7\. Patients with multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); * 8\. Accompanied by pleural effusion or ascites, causing respiratory syndrome (≥CTC AE level 2 dyspnea); * 9\. 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 * 10\. Receive major surgical treatment, open biopsy or significant traumatic injury within 28 days before grouping; * 11\. 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; * 12\. 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; * 13\. Occurrence of ARTERIAL/venous thrombotic events, such as cerebrovascular accidents (including temporary ischemic attacks), deep venous thrombosis and pulmonary embolism within 6 months; * 14\. Persons with a history of abuse of psychotropic substances and who cannot be cured or have mental disorders; * 15\. Pregnant and lactating women; * 16\. Participated in other clinical trials of anti-tumor drugs within 4 weeks; * 17\. The researcher considered that there were other conditions that were not suitable for inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progress free survival (PFS) for phase Ⅱ | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization until death (up to 30 months) | OS is defined as the time until death due to any cause. |
| Objective Response Rate (ORR) | each 42 days up to intolerance the toxicity or PD (up to30 months) | ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy. |
Countries
China
Outcome results
None listed