Study of Anlotinib Plus Chemoradiotherapy in Patients With Locally Advanced NSCLC

• Status: Unknown status
• Trial end date: 2021-05-17
• Target enrollment: 0
• Participant gender: All

Summary

Lung cancer is the most common cancer, accounting for 20% of cancer-related deaths worldwide. In 2015, an estimated 610,200 patients (22 per cent of cancer-related deaths) died of lung cancer. Non-small cell lung cancer ((NSCLC)) accounts for 80% to 85% of lung cancer. Most patients are locally advanced or metastatic diseases at the time of diagnosis. Some IIIA tumors are considered resectable, but many IIIA (with larger N2) and IIIB (T4, any NM0, any TN3M0) are not considered suitable for surgery. Since the 1990s, simultaneous radiotherapy and chemotherapy ((CHRT)) has become the cornerstone of (NSCLC) in locally advanced non-small cell lung cancer (NSCLC). At present, there is no clinical evidence of survival benefits of synchronous radiotherapy plus TKI targeted therapy for unresectable stage Ⅲ A and stage Ⅲ B non-small cell lung cancer. However, a HELPER STUDY study was conducted to evaluate the efficacy and safety of continuous intravenous infusion combined with EP regimen plus concurrent radiotherapy in the treatment of unresectable stage Ⅲ NSCLC. The median survival time was 34.7 months and the 3-year survival rate was 47.7%. Anlotinib capsule is a small molecule multi-target tyrosine kinase inhibitor. This is a single group partitioned, multicenter, exploratory clinical study to observe and evaluate the safety and tolerance of anlotinib hydrochloride combined with cisplatin plus etoposide or pemetrexed in the treatment of locally advanced NSCLC patients. To determine the maximum tolerable dose of (MTD) and / or stage II clinical recommended dose (RP2D) and evaluate its preliminary efficacy. In the first stage of this study, 12 patients with locally advanced NSCLC were divided into 3 experimental groups. After taking three different doses of anlotinib combined with platinum simultaneous radiotherapy, the dose limited toxicity was observed, and the maximum tolerable dose was determined in the second stage. 78 patients were enrolled according to RP2D, and the indexes such as ORR were evaluated. To evaluate the safety and efficacy of anlotinib combined with platinum-containing simultaneous radiotherapy in the treatment of locally advanced NSCLC.

Anlotinib (D1-14, d22-36, followed by a 21-day cycle, taking medicine for 2 weeks, stopping for 1 week).

Group 1: 8mg po qd, Group 2: 10mg po qd, Group 3: 12mg po qd;

Combined chemotherapy:

Cisplatin + etoposide Or PC: carboplatin AUC2, paclitaxel 45-50 mg 2 per week; Cisplatin + pemetrexed (non-squamous cell carcinoma). Simultaneous radiotherapy: 3D-CRT or IMRT external radiotherapy (60-66 Gy, 2.0 Gy / day).

The curative effect was evaluated after 6 weeks of simultaneous radiotherapy and chemotherapy combined with alotinib, and then the efficacy of alotinib or chemotherapy was maintained until PD.

Main outcome measures:

Phase I main outcome measures: maximum tolerated dose (MTD), dose limited toxic (DLT).

Main indicators of II: objective remission rate (ORR). Secondary indicators: disease control rate (DCR), progression-free survival (PFS)

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
• Collaborators: First Affiliated Hospital Xi'an Jiaotong University; Shaanxi Provincial Cancer Hospital; Shaanxi Provincial People's Hospital; Tang-Du Hospital; Xijing Hospital

Criteria

Inclusion Criteria:

1. Age: 18 to 70 years old; two。. Histologically or cytologically confirmed, locally advanced IIIA 、IIIB or IIIC NSCLC (according to version 8); 3.ECOG score: 0-1; 4. Those who have not received targeted and immunotherapy in the past; 5. Patients who had not undergone surgery in the past; 6. The damage caused by other treatments was recovered, in which the interval of receiving nitroso or mitomycin was ≥ 6 weeks, receiving other cytotoxic drugs and bevacizumab (Avastin) ≥ 4 weeks; 7. The function of the main organs is normal, that is, the following criteria are met:

1. the standard of blood routine examination should be met (no blood transfusion and blood products within 14 days, not corrected by G-CSF and other hematopoietic stimulating factors): A. HB ≥ 90g; B. ANC ≥ 1.5 × 109; C. PLT ≥ 80 × 109;

2. biochemical tests shall meet the following criteria: A. TBIL < 1.5ULN; B. ALT and AST < 2.5ULN; c. Serum Cr ≤ 1.5ULN or endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); 8. Doppler Echocardiography: left Ventricular ejection fraction (LVEF) ≥ 50% normal Lower limit (LLN).

9. The subjects volunteered to join the study and signed an informed consent form with good compliance and follow-up.

Exclusion Criteria:

1. Small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer); The patients with positive mutations of 2.EGFR, ALK and ROS1 genes were feasible for targeted therapy.

3. In the past, more than 4 cycles of chemotherapy were received. 4. Hemoptysis in patients with non-small cell lung cancer (> 50 mL / day), tumor with cavity or necrosis; 5. The imaging showed that the important blood vessels had been invaded by the tumor or the researchers determined that the tumor might invade the important blood vessels during the follow-up period and cause fatal bleeding.

6. Those with hypertension and could not be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);) had a history of unstable angina pectoris. Patients with newly diagnosed angina pectoris within 3 months before screening or myocardial infarction events within 6 months before screening, arrhythmias (including QTcF ≥ 470 ms) required long-term use of antiarrhythmic drugs and New York Heart Association grade ≥ II cardiac insufficiency.

7. It has obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction.

8. Patients with abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+ 4 seconds or APTT > 1.5 ULN),) had bleeding tendency or were treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues. On the premise that the international standardized ratio of prothrombin time (INR) ≤ 1.5, low dose heparin (6000U / d for adults) or low dose aspirin (not exceeding 100U / d) is allowed.

9. Urine routine showed that urinary protein ≥ + +, or 24-hour urinary protein quantity ≥ 1.0g; 10. The bleeding symptoms in the first 3 months have obvious clinical significance or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic ulcer, positive fecal occult blood, etc.

11. There were venous thromboembolism events in the first 12 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism.

twelve。. The patients participated in clinical trials of other antineoplastic drugs within 4 weeks.

The researchers judged other situations that may affect the conduct of clinical studies and the determination of the results of the studies.