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Osimertinib Combined With Anlotinib in EGFR T790M Mutated NSCLC Patients With Progression on Osimertinib Treatment

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ClinicalTrials.gov Identifier: NCT04438902
Recruitment Status : Not yet recruiting
First Posted : June 19, 2020
Last Update Posted : June 19, 2020
Sponsor:
Information provided by (Responsible Party):
First Affiliated Hospital of Zhejiang University

Brief Summary:
EGFR T790M gatekeeper mutation accounts for approximately 60% of acquired resistance to the first- or second-generation EGFR-TKI treatment. Osimertinib, a third-generation EGFR TKI, has become the standard therapy for NSCLC patients with acquired EGFR T790M mutation. However, acquired resistance to osimertinib is still inevitable and there is no established targetable agent currently. Thus, treatment strategy for patients with acquire resistance to osimertinib remains an urgent issue. In this study, we aimed to evaluate the efficacy of osimertinib combined with anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib treatment.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: osimertinib mesylate tablets and anlotinib hydrochloride capsules Phase 2

Detailed Description:

In current clinical practice, acquired resistance to osimertinib can be divided into three clinical modes: dramatic progression, gradual progression and local progression. For patients with gradual progression,there are various clinical explorations,including the continuation of osimertinib with chemotherapy or radiotherapy, osimertinib combined with antiangiogenic agents. In preclinical studies, an overactive vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathway and tumour angiogenesis plays a crucial role in the resistance to EGFR-TKIs, and the dual targeting of both the VEGF and EGFR pathways may prevent resistance.

Anlotinib (AL3818) is an inhibitor targeting multiple receptor tyrosine kinases involved in tumour progression, especially VEGFR 2/3, PDGFRα/β and c-Kit. We suppose that the combination treatment of osimertinib and anlotinib may ameliorate acquired resistance to osimertinib.This is a multi-center, open, single-arm, exploratory phase 2 trial evaluating osimertinib combined with anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a multi-center, open, single-arm, exploratory phase 2 trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Multi-center, Interventional Study of Osimertinib Combined With Anlotinib in Acquired EGFR T790M Mutated NSCLC Patients With Gradual Progression on Osimertinib Treatment
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: osimertinib combined with anlotinib Drug: osimertinib mesylate tablets and anlotinib hydrochloride capsules
osimertinib mesylate tablets 80mg qd and anlotinib hydrochloride capsules 10mg qd day 1-14 of a 21-day cycle
Other Name: TAGRISSO and FOCUS V




Primary Outcome Measures :
  1. progression-free survival (PFS) [ Time Frame: from the date of first dose of osimertinib until the date of disease progression,assessed up to 12 months. ]
    PFS is defined as the time from beginning of osimertinib to disease progression on combination treatment of osimertinib and anlotinib.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks. ]
    Objective Response Rate (ORR), is defined as the percentage of patients with complete response or partial response by investigator assessment as recorded in the CRF, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 in clinical practice.

  2. Disease Control Rate (DCR) [ Time Frame: from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks. ]
    Disease Control Rate (DCR), is defined as the percentage of patients with complete response or partial response or stable disease by investigator assessment as recorded in the CRF, which usually refer to RECIST v1.1 in clinical practice.

  3. Adverse events/Serious adverse events [ Time Frame: From signing ICF to 30 days after the end of treatment. ]
    Incidence of Adverse Events (AEs): Incidence, severity and seriousness of adverse events, incidence of serious adverse events (SAEs), which usually be graded by CTCAE v5.0 based on current clinical practice.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to provide informed consent, complete all study assessments and have complete medical record.
  2. Age:18-75 years.
  3. Histologically or cytologically confirmed diagnosis of local advanced or metastatic NSCLC.
  4. Patients should be confirmed acquired EGFR T790M mutation and received osimertinib as the second line treatment, and they should have the following: (1) benefit from treatment with osimertinib initially ;(2) gradual progression on osimertinib treatment as defined by minor increment of tumor burden (≥10% but <20% in the sum of target lesions).
  5. At least one measurable lesion as defined by lesions ≥10mm in long axis according to RECIST 1.1.

Exclusion Criteria:

  1. Patients who will be or were involved in any other interventional antitumour clinical studies for locally advanced/metastatic NSCLC currently or previously.
  2. Small cell lung cancer (including small lung cancer mixed with non-small cell lung cancer).
  3. Patients at risk of bleeding.
  4. Patients with renal dysfunction.
  5. Uncontrolled severe hypertension.
  6. Any concomitant condition evaluated by physicians which is not suitable for osimertinib or anlotinib treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04438902


Contacts
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Contact: Yuehong Wang 13989826233 yuehongw@zju.edu.cn
Contact: Shan Lu 137 5822 2639

Locations
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China, Zhejiang
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, China, 310003
Contact: Yuehong Wang, MD    13989826233    yuehongw@zju.edu.cn   
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang, China, 310014
Contact: Liqin Lu    13858039628      
The First Affiliated Hospital of Jiaxing College
Jiaxing, Zhejiang, China, 314001
Contact: Qi Zhang    13957382862      
Sponsors and Collaborators
First Affiliated Hospital of Zhejiang University
Investigators
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Principal Investigator: Yuehong Wang First Affiliated Hospital of Zhejiang University
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Responsible Party: First Affiliated Hospital of Zhejiang University
ClinicalTrials.gov Identifier: NCT04438902    
Other Study ID Numbers: TRAIN
First Posted: June 19, 2020    Key Record Dates
Last Update Posted: June 19, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share participant data of the trial.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by First Affiliated Hospital of Zhejiang University:
non-small-cell lung cancer
EGFR T790M
osimertinib
anlotinib
acquired resistance
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action