Study of Anlotinib Plus Chemotherapy as the First-line Treatment in Patients With Advanced NSCLC

Study Overview
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Brief Summary
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Non-small cell lung cancer has the highest morbidity and mortality in China，and platinum-based chemotherapy is the standard first-line treatment for the wild-type NSCLC,however the overall survival still less than one year.Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2、VEGFR3、PDGFRβ and c-Kit, which has strong effect of anti-angiogenesis.This study is aim to evaluate the efficacy and safety of the combination regimen of anlotinib plus platinum-based chemotherapy as first-line treatment for NSCLC.

Official Title
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A Phase I/II Study of Anlotinib Combined With Platinum-based Chemotherapy as the First-line Treatment of Patients With Locally Advanced or Advanced Non-Small Cell Lung Cancer

Conditions
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NSCLC, Adenocarcinoma, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Anlotinib combined with pemetrexed and carboplatin, phase I
* Drug: Anlotinib combined with paclitaxel and carboplatin, phase I
* Drug: Anlotinib combined with pemetrexed and carboplatin, phase II
* Drug: Anlotinib combined with paclitaxel and carboplatin, phase II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age：18 70 years; Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2 Subjects with histologically or cytologically confirmed locally advanced or advanced NSCLC EGFR\ALK\ROS1 wildtype or unknown,or patients with EGFR\ALK\ROS1 mutations but refuse to receive corresponding inhibitors' treatment No indications for radiation therapy Previously chemotherapy naive or postoperative adjuvant chemotherapy ended more than 1 year Subjects with at least one measurable lesion as defined by RECIST (version 1.1),which is confirmed by computed tomography (CT) scan or MRI Exclusion Criteria: Small Cell Lung Cancer central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day) Within 30 days before enrollment, the patient had used any chemotherapy drugs in the previous treatment regimen or clinical study; Or, within 14 days before the first administration of the study therapy, the patient has used any targeted anticancer drugs in the previous treatment regimen or clinical study; Or stop other experimental drugs or cancer drugs for less than five half-life of the drug Previous use of anti-angiogenic drugs (such as anlotinib, apatinib, bevacizumab, endostar, etc.) have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included Spinal cord compression or symptomatic and untreated brain metastases (asymptomatic, stable, no need for steroid treatment for 4 weeks before study start) with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus) Previous histories include: interstitial pneumonia, drug-induced interstitial pneumonia, radiation pneumonia requiring steroid treatment, and clinically proven active interstitial pneumonia get arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), prevenous thrombosis, and pulmonary embolism Have suffered from hemorrhagic disease or coagulation dysfunction diagnosed with disease which will severely endanger the security of patients or influence the completion of this research

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-squamous cell lung cancer<br>Anlotinib combined with pemetrexed and carboplatin, phase I Anlotinib combined with pemetrexed and carboplatin, phase II | Drug: Anlotinib combined with pemetrexed and carboplatin, phase I<br>* Non-squamous cell lung cancer, Anlotinib Plus PC This study will include a sequential evaluation of 3 subjects per dose group. low-dose groups: Anlotinib 8mg per day plus pemetrexed and carboplatin. middle-dose groups: Anlotinib 10mg per day plus pemetrexed and carboplatin. high-dose groups: Anlotinib 12mg per day plus pemetrexed and carboplatin to determine the appropriate dose of anlotinib in combination with paclitaxel and carboplatin<br>* Other names: APC I;Drug: Anlotinib combined with pemetrexed and carboplatin, phase II<br>* Anlotinib: established dose QD PO d1-14, pemetrexed,carboplatin, 21 days per cycle after 4-6 cycles, Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent<br>* Other names: APCII;|
| Experimental: Squamous cell lung cancer<br>Anlotinib combined with paclitaxel and carboplatin, phase I Anlotinib combined with paclitaxel and carboplatin, phase II | Drug: Anlotinib combined with paclitaxel and carboplatin, phase I<br>* Squamous cell lung cancer, Anlotinib plus TC This study will include a sequential evaluation of 3 subjects per dose group. low-dose groups: Anlotinib 8mg per day plus paclitaxel and carboplatin. middle-dose groups: Anlotinib 10mg per day plus paclitaxel and carboplatin. high-dose groups: Anlotinib 12mg per day plus paclitaxel and carboplatin to determine the appropriate dose of anlotinib in combination with paclitaxel and carboplatin<br>* Other names: ATC I;Drug: Anlotinib combined with paclitaxel and carboplatin, phase II<br>* Anlotinib :established dose QD PO d1-14, paclitaxel,carboplatin, 21 days per cycle after 4-6 cycles, Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent<br>* Other names: ATCII;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival (PFS) | progression free survival | From date of enrollment until the date of first documented progression or date of death from any cause,whichever came first.up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate | each 21 days up to the toxicity or PD (up to 24 months) | 
| Disease Control Rate (DCR) | Disease Control Rate | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Overall Survival (OS) | Overall survival | From enrollment until death (up to 36 months) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability (Safety) | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Time Frame: each 21 days up to the toxicity or PD (up to 36 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anlotinib, NSCLC, platinum-based chemotherapy