Clinical trial NCT04958993: A Trial of Anlotinib Combined With Concurrent Chemoradiotherapy in Patients With Unresectable Stage III Non-small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2021-07-12
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progress free survival (PFS) for phase Ⅱ
timeFrame: up to 30 months
measure: Maximum Tolerance Dose (MTD) for phaseⅠ
timeFrame: From enrollment to completion of study. Estimated about 18months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 30 months)
measure: Objective Response Rate (ORR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to30 months)
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: JINGMIN YU, PhD
role: PRINCIPAL_INVESTIGATOR
References: