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Armatinib Alone or in Combination With SRT for Brain Metastases EGFR-mutated Non-small Cell Lung Cancer

Primary Purpose

Non-small Cell Lung Cancer Metastatic

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Almonertinib
SBRT
Sponsored by
Shanghai Cancer Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer Metastatic

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: aged 18 years or older (including 18 years) and up to 75 years (including 75 years) histologically confirmed NSCLC (by AJCC 8th edition lung cancer staging criteria) asymptomatic or minimally symptomatic brain metastases (i.e., headache, nausea, or seizures responding to dexamethasone/analgesic/antiepileptic agents at a stable drug dose for at least 3 days); brain metastases must meet the following criteria on diagnostic MRI: at least one lesion that can be classified as measurable disease according to RANO-BM, ≤ 10 brain or brainstem metastases epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation (alone or in combination with other EGFR mutations); no prior systemic therapy other than neoadjuvant therapy, adjuvant therapy, or concurrent chemotherapy for more than 3 months prior to study entry Eastern Cooperative Oncology Organization Group (ECOG) physical status score of 0 or 1 and no worsening in the previous 2 weeks, with a minimum expected survival of 12 weeks. good hematopoietic function, defined as absolute neutrophil count ≥ 1.5 × 109 /L, platelet count ≥ 100 × 109 /L, and hemoglobin ≥ 90 g/L [no transfusion or erythropoietin (EPO-dependent) within 7 days good coagulation, defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is on anticoagulation therapy, as long as the PT is within the proposed range of anticoagulant medication good liver function, defined as a total bilirubin level ≤ 1.5 times the upper limit of normal (ULN); glutathione transaminase (AST) and glutamate transaminase (ALT) levels ≤ 2.5 times the ULN for patients without liver metastases; and AST and ALT levels ≤ 5 times the ULN for patients with documented liver metastases good renal function, defined as serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 60 ml/min; urine protein less than 2+ on routine urine examination, or 24-hour urine protein quantification < 1 g Women of childbearing potential should have a negative urine or serum pregnancy test within 3 days prior to receiving the first dose of study drug (Week 1, Day 1). male patients should be using barrier contraception (i.e., condoms) from screening until 6 months after discontinuation of study treatment Subjects will voluntarily participate and sign an informed consent in writing. Exclusion Criteria: Received any of the following treatments: Currently participating in an interventional clinical study treatment or received another study drug within 4 weeks prior to the first dose Received palliative intracranial radiation therapy prior to the first dose Patient has undergone major surgery (including biopsy) or major trauma within 4 weeks prior to the first dose of study drug; patients who are expected to require major surgery during the study period Patients previously treated with EGFR-TKI. patients with NSCLC EGFR driver gene negative or known severe allergic reactions (≥ grade 3) to TKIs drugs; patients who are unable to undergo MR examination brain metastases requiring surgical decompression; the presence of a previous solid organ or hematologic transplant; clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction; the presence of clinically uncontrollable pleural effusion/peritoneal effusion malignancy other than non-small cell lung cancer within 5 years prior to enrollment, excluding adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer of the skin, localized prostate cancer after radical surgery, and ductal carcinoma in situ of the breast; having unremitting residual toxicity of prior therapy greater than CTCAE grade 1 at the time of initiation of study treatment, with the exception of alopecia and grade 2 neurotoxicity from prior chemotherapy; have any serious or poorly controlled systemic disease, such as active bleeding-prone body or active infection, as judged by the investigator. Chronic illnesses that do not require exclusion; the known presence of a psychiatric illness or substance abuse condition that may have an impact on compliance with trial requirements any serious or uncontrolled ocular pathology that, in the judgment of the physician, may increase the safety risk to the patient a known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive) patients who, in the judgment of the investigator, are likely to be poorly compliant with the procedures and requirements of the study.

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

GroupA

GroupB

GroupC

Arm Description

Intracranial stereotactic radiotherapy (27-40 Gy/3-5f) was administered to all intracranial lesions on the first day of oral administration of Almonertinib

Two successive MR enhancements after oral administration of Almonertinib suggest that intracranial lesions are maximally remission, and stereotactic body radiotherapy is given to all lesions (27-40Gy/3-5f)

oral administration of Almonertinib

Outcomes

Primary Outcome Measures

iPFS
Intracranial to time to disease progression

Secondary Outcome Measures

Full Information

First Posted
March 23, 2023
Last Updated
March 23, 2023
Sponsor
Shanghai Cancer Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05800223
Brief Title
Armatinib Alone or in Combination With SRT for Brain Metastases EGFR-mutated Non-small Cell Lung Cancer
Official Title
Prospective, Multicenter, Randomized Controlled, Phase III Clinical Study of Armatinib Alone or in Combination With Stereotactic Body Radiotherapy (SRT) for First-line Treatment of Brain Metastases From EGFR-mutated Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Actual)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Cancer Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Objective:Patients with asymptomatic or minimally symptomatic Stage IV EGFR-positive NSCLC with baseline intracranial metastases. Aim: To investigate the timing, efficacy and safety of radiotherapy in patients with EGFR positive brain metastases treated with armatinib alone or combined with stereotactic radiotherapy. Method: Almonertinib: specification 55mg/tablet; The dosage is 110 mg / day (2 tablets / day) orally once a day; SBRT: 3-5 doses of 27-40 Gy

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GroupA
Arm Type
Experimental
Arm Description
Intracranial stereotactic radiotherapy (27-40 Gy/3-5f) was administered to all intracranial lesions on the first day of oral administration of Almonertinib
Arm Title
GroupB
Arm Type
Experimental
Arm Description
Two successive MR enhancements after oral administration of Almonertinib suggest that intracranial lesions are maximally remission, and stereotactic body radiotherapy is given to all lesions (27-40Gy/3-5f)
Arm Title
GroupC
Arm Type
Experimental
Arm Description
oral administration of Almonertinib
Intervention Type
Drug
Intervention Name(s)
Almonertinib
Intervention Description
The dosage is 110 mg/day (2 tablets/day) orally once a day
Intervention Type
Radiation
Intervention Name(s)
SBRT
Intervention Description
SRT, 27Gy-40Gy/3-5f
Primary Outcome Measure Information:
Title
iPFS
Description
Intracranial to time to disease progression
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: aged 18 years or older (including 18 years) and up to 75 years (including 75 years) histologically confirmed NSCLC (by AJCC 8th edition lung cancer staging criteria) asymptomatic or minimally symptomatic brain metastases (i.e., headache, nausea, or seizures responding to dexamethasone/analgesic/antiepileptic agents at a stable drug dose for at least 3 days); brain metastases must meet the following criteria on diagnostic MRI: at least one lesion that can be classified as measurable disease according to RANO-BM, ≤ 10 brain or brainstem metastases epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation (alone or in combination with other EGFR mutations); no prior systemic therapy other than neoadjuvant therapy, adjuvant therapy, or concurrent chemotherapy for more than 3 months prior to study entry Eastern Cooperative Oncology Organization Group (ECOG) physical status score of 0 or 1 and no worsening in the previous 2 weeks, with a minimum expected survival of 12 weeks. good hematopoietic function, defined as absolute neutrophil count ≥ 1.5 × 109 /L, platelet count ≥ 100 × 109 /L, and hemoglobin ≥ 90 g/L [no transfusion or erythropoietin (EPO-dependent) within 7 days good coagulation, defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is on anticoagulation therapy, as long as the PT is within the proposed range of anticoagulant medication good liver function, defined as a total bilirubin level ≤ 1.5 times the upper limit of normal (ULN); glutathione transaminase (AST) and glutamate transaminase (ALT) levels ≤ 2.5 times the ULN for patients without liver metastases; and AST and ALT levels ≤ 5 times the ULN for patients with documented liver metastases good renal function, defined as serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 60 ml/min; urine protein less than 2+ on routine urine examination, or 24-hour urine protein quantification < 1 g Women of childbearing potential should have a negative urine or serum pregnancy test within 3 days prior to receiving the first dose of study drug (Week 1, Day 1). male patients should be using barrier contraception (i.e., condoms) from screening until 6 months after discontinuation of study treatment Subjects will voluntarily participate and sign an informed consent in writing. Exclusion Criteria: Received any of the following treatments: Currently participating in an interventional clinical study treatment or received another study drug within 4 weeks prior to the first dose Received palliative intracranial radiation therapy prior to the first dose Patient has undergone major surgery (including biopsy) or major trauma within 4 weeks prior to the first dose of study drug; patients who are expected to require major surgery during the study period Patients previously treated with EGFR-TKI. patients with NSCLC EGFR driver gene negative or known severe allergic reactions (≥ grade 3) to TKIs drugs; patients who are unable to undergo MR examination brain metastases requiring surgical decompression; the presence of a previous solid organ or hematologic transplant; clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction; the presence of clinically uncontrollable pleural effusion/peritoneal effusion malignancy other than non-small cell lung cancer within 5 years prior to enrollment, excluding adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer of the skin, localized prostate cancer after radical surgery, and ductal carcinoma in situ of the breast; having unremitting residual toxicity of prior therapy greater than CTCAE grade 1 at the time of initiation of study treatment, with the exception of alopecia and grade 2 neurotoxicity from prior chemotherapy; have any serious or poorly controlled systemic disease, such as active bleeding-prone body or active infection, as judged by the investigator. Chronic illnesses that do not require exclusion; the known presence of a psychiatric illness or substance abuse condition that may have an impact on compliance with trial requirements any serious or uncontrolled ocular pathology that, in the judgment of the physician, may increase the safety risk to the patient a known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive) patients who, in the judgment of the investigator, are likely to be poorly compliant with the procedures and requirements of the study.
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Fan, MD
Phone
8602164175590
Email
fanming@fudan.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Armatinib Alone or in Combination With SRT for Brain Metastases EGFR-mutated Non-small Cell Lung Cancer

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