Clinical trial NCT03636685: Study of Anlotinib Plus Chemotherapy as the First-line Treatment in Patients With Advanced NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: NSCLC
Adenocarcinoma
Squamous Cell Carcinoma
Keywords: Anlotinib
NSCLC
platinum-based chemotherapy
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2018-08-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progress free survival (PFS)
timeFrame: 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 outcomes:
measure: Objective Response Rate (ORR)
timeFrame: each 21 days up to the toxicity or PD (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Overall Survival (OS)
timeFrame: From enrollment until death (up to 36 months)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability (Safety)
timeFrame: Time Frame: each 21 days up to the toxicity or PD (up to 36 months)
Other outcomes:
Locations:
Study officials:
References:
citation: Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.