Study of Anlotinib Plus Chemoradiotherapy in Patients With Locally Advanced NSCLC

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)

Conditions

• Patients With Non-small Cell Lung Cancer

Interventions

DRUG

Simultaneous chemoradiotherapy for An Luo

Experimental group: anlotinib(d1-14, d22-36), followed by 21 days period, 2 weeks medication, 1 week maintenance therapy. . Group II: 10 mg po qd, Group III: 12 mg po qd; Combined chemotherapy: Cisplatin + etoposide Or PC: carboplatin AUC2, paclitaxel 45-50 mg 2 per week; Cisplatin + cultured beauty (non squamous cell carcinoma). Synchrotron radiation: radiotherapy combined with radiotherapy (3D-CRT or IMRT) (60-66Gy / 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.

Sponsors & Collaborators

• Tang-Du Hospital

  collaborator OTHER

• Xijing Hospital

  collaborator OTHER

• First Affiliated Hospital Xi'an Jiaotong University

  collaborator OTHER

• Shaanxi Provincial Cancer Hospital

  collaborator OTHER

• Shaanxi Provincial People's Hospital

  collaborator OTHER

• Second Affiliated Hospital of Xi'an Jiaotong University

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-11-22

Primary Completion

2021-05-17

Completion

2021-05-17

Countries

• China

Study Locations