Adenocarcinoma, NSCLC, Squamous Cell Carcinoma
Conditions
Keywords
Anlotinib, NSCLC, platinum-based chemotherapy
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.
Interventions
DRUGAnlotinib combined with pemetrexed and carboplatin, phase I
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
DRUGAnlotinib combined with paclitaxel and carboplatin, phase I
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
DRUGAnlotinib combined with pemetrexed and carboplatin, phase II
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
DRUGAnlotinib combined with paclitaxel and carboplatin, phase II
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
Sponsors
Chinese Academy of Medical Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progress free survival (PFS) | 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 | progression free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | each 21 days up to the toxicity or PD (up to 24 months) | Objective Response Rate |
| Disease Control Rate (DCR) | each 42 days up to intolerance the toxicity or PD (up to 24 months) | Disease Control Rate |
| Overall Survival (OS) | From enrollment until death (up to 36 months) | Overall survival |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability (Safety) | Time Frame: each 21 days up to the toxicity or PD (up to 36 months) | Number of Participants with Adverse Events as a Measure of Safety and Tolerability |
Contacts
Primary ContactYuankai Shi, MD
Backup ContactZhaoyuan Shi
Outcome results
None listed