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

NSCLC Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03636685
• Other study ID #: NCC201807006
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: August 15, 2018
• Est. completion date: August 14, 2020

Study information

• Verified date: August 2018
• Source: Chinese Academy of Medical Sciences
• Contact: Yuankai Shi, MD
• Phone: +86 13701251865
• Email: syuankaipumc[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: August 14, 2020
• Est. primary completion date: August 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Squamous Cell
• NSCLC
• Squamous Cell Carcinoma

Intervention

Drug:
• Anlotinib 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
• Anlotinib 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
• Anlotinib 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
• Anlotinib 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

References & Publications (1)

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 (ALT — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective Response Rate (ORR)	Objective Response Rate	each 21 days up to the toxicity or PD (up to 24 months)
Secondary	Disease Control Rate (DCR)	Disease Control Rate	each 42 days up to intolerance the toxicity or PD (up to 24 months)
Secondary	Overall Survival (OS)	Overall survival	From enrollment until death (up to 36 months)
Secondary	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)