A Multi-center, One-arm, Phase II Trial of Anlotinib Combined With Osimertinib as the Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M.

Tianjin Medical University Cancer Institute and Hospital4 sites in 1 country53 target enrollmentJuly 31, 2019

ConditionsNon Small Cell Lung Cancer

InterventionsAnlotinib Combined With Osimertinib

DrugsAnlotinib Combined With Osimertinib

Overview

Phase: Phase 2
Intervention: Anlotinib Combined With Osimertinib
Conditions: Non Small Cell Lung Cancer
Sponsor: Tianjin Medical University Cancer Institute and Hospital
Enrollment: 53
Locations: 4
Primary Endpoint: Progression-free survival (PFS)
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations.

Detailed Description

Anlotinib Hydrochloride is a kind of innovative medicines approved by State Food and Drug Administration（CFDA:2011L00661） which was developed by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β and c-Kit.

Registry

clinicaltrials.gov

Start Date

July 31, 2019

End Date

November 30, 2021

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Tianjin Medical University Cancer Institute and Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed, locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC or recurrent non-squamous NSCLC (according to the 8th Edition of the AJCC Staging system).
•Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing.
•Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent first- or second-generation EGFR TK treatment regimen.
•18-75years，ECOG PS：0-2，Life expectancy of more than 3 months，with measurable lesion ( RECIST1.1).
•≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction；Previously received radiation therapy, but the radiotherapy area must be \<25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment.
•Main organs function is normal.
•Signed and dated informed consent.
•The woman patients of childbearing age must agree to take contraceptive methods during the research and within another 8 weeks after treatment. Pregnancy test (blood serum test or urine) should be done within 7 days before the research and the result should be negative.The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after treatment.

Exclusion Criteria

•Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
•Non-small cell lung cancer (NSCLC) with an EGFR C797S mutation.
•Prior treatment with a third-generation EGFR TKI (i.e. Rociletinib, Olmutinib、BPI-15086、BPI-7711、Osimertinib); Prior treatment with agents targeting the VEGF pathway, including bevacizumab and Anlotinib.
•Treatment with an EGFR TKI (i.e. erlotinib, gefitinib or afatinib) within 8 days or approximately 5 x half-life, whichever is longer, of the first dose of study treatment；Patients may not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within five half-lives of the compound or 3 months, whichever is greater
•Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 platinum-therapy related neuropathy
•Any factor that would preclude adequate absorption of Osimertinib and Anlotinib, including refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection
•Patients with obvious brain metastases, cancerous meningitis, spinal cord compression, or with brain or pia mater disease. (patient with brain metastases who have completed treatment 28 days before and the symptoms are stable can be Enrolled, also should have no cerebral hemorrhage symptoms confirmed by brain MRI, CT or venography evaluation
•Patients who planned to receive systemic anti-tumor therapy within 4 weeks prior to allocation or during the course of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or receiving the Mitomycin C 6 weeks prior to medication). Extra-field radiotherapy (EF-RT) was performed 4 weeks prior to allocation or restricted radiotherapy for assessing tumor lesions within 2 weeks prior to allocation
•Patients with any severe and/or uncontrolled disease, including:
•Inadequately controlled hypertension (HTN) (systolic blood pressure \[SBP\] \> 140 mmHg and/or diastolic blood pressure \[DBP\] \> 90 mmHg despite antihypertensive medication)

Arms & Interventions

Anlotinib Combined With Osimertinib

Anlotinib 12 mg once a day from day 1 to 14 of a 21-day cycle. Osimertinib 80mg p.o, qd. It should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent.

Intervention: Anlotinib Combined With Osimertinib

Outcomes

Primary Outcomes

Progression-free survival (PFS)

Time Frame: each 42 days up to PD or death (up to 24 months)

The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

Secondary Outcomes

ORR（Objective Response Rate）(each 42 days up to intolerance the toxicity or PD (up to 24 months))
Adverse Events(Until 30 day safety follow-up visit)
OS（Overall Survival）(up to 24 months)
DCR（Disease Control Rate）(each 42 days up to intolerance the toxicity or PD (up to 24 months))