Trial Title:
Ensartinib in Combination With Bevacizumab in ALK-positive NSCLC Patients With TP53 Mutation
NCT ID:
NCT05491811
Condition:
Non-Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Bevacizumab
Ensartinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ensartinib
Description:
Participants will receive Ensartinib 225 mg oral once daily from baseline until disease
progression, unacceptable toxicity, withdrawal of consent or death.
Arm group label:
Ensartinib and Bevacizumab
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Participants will receive 7.5 mg/kg intravenous on Day 1 of 21 day cycles (every 3 weeks)
from baseline until disease progression, unacceptable toxicity, withdrawal of consent or
death.
Arm group label:
Ensartinib and Bevacizumab
Other name:
MIL60
Summary:
This is a prospective, single-arm, multicenter, phase II study to investigate the
efficacy and safety of Ensartinib plus Bevacizumab in metastatic anaplastic lymphoma
kinase (ALK)-rearranged Non-Small Cell Lung Cancer (NSCLC) with TP53 mutation.
Detailed description:
Patients with advanced or metastatic NSCLC with ALK positive and TP53 mutation were
clinically confirmed. Medical history collection, physical examination, laboratory
examination, concomitant diseases and medication records were taken according to the
patient's diagnosis and treatment. Laboratory examination included but not limited to
blood routine and blood biochemical examination. To determine whether patients were
suitable for treatment with Ensartinib combined with Bevacizumab according to the entry
and exclusion criteria. For patients who met the prescription, blood samples were
collected within 1 week before medication. Imaging examination was performed every 6
weeks (±7 days) in the first 2 years and every 12 weeks (±7 days) in the second 2 years.
Examination items included chest CT, head MRI; See if additional tests (e.g., bone scan,
total abdominal augmentation) are needed based on the actual clinical situation. When the
disease progresses, blood samples should be collected within 4 weeks after the disease
progression, and if possible, tumor tissues of the progressive lesions after the disease
progression should be collected. Patients can choose to continue to use the regimen
recommended by the doctor if the doctor considers that the use of Ensartinib therapy or
combination therapy may still bring benefit to the patient. The follow-up treatment plan,
the best efficacy evaluation, and the duration of treatment were recorded. When the end
point of follow-up was reached, that is, the patient died or was lost to follow-up, the
date of death or loss and the main causes should be tracked and recorded in detail.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed advanced (stage IIIB) or metastatic (stage
IV) NSCLC;
- ALK positive with TP53 mutation was confirmed by tissue samples or blood in each
center; TP53 mutation detection needs to be confirmed by NGS. ALK positive can be
detected by NGS,IHC,RT-PCR and FISH;
- Age ≥ 18 years old;
- ALK-TKI-naive patients, and allowed to have received at most one line previous
chemotherapy;
- ECOG Performance status (PS) score is 0-2;
- Karnofsky Performance Status of ≥70;
- Subjects with CNS metastases are only eligible if the CNS metastases are adequately
treated with radiotherapy and/or surgery and subjects are neurologically returned to
baseline (except for residual signs or symptoms related to the CNS treatment) for at
least 1 week prior to randomization.
A.Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3
weeks for neurological stabilization before randomization.
B.This exception does not include carcinomatous meningitis which is excluded regardless
of clinical stability.
- Life expectancy of at least 12 weeks;
- Able to swallow oral drugs;
- It has certain organ system functions, defined as follows:
A. Absolute neutrophil count (ANC) ≥1.5 x 109/L B. Platelets ≥100 x 109/L C. hemoglobin
≥9 g per deciliter (≥90g per liter) note that blood transfusions are permitted to achieve
the required hemoglobin level.
D. Total bilirubin ≤1.5 times upper limit of normal (ULN) E. In the absence of liver
metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN;
In case of liver metastasis, ≤5×ULN.
F. Creatinine ≤1.5 x ULN. If ≥ 1.5 × ULN and creatinine clearance value calculated by
Cockcroft-Gault method ≥ 50 mL/min (0.83 mL/s), patients were still eligible for
inclusion.
- Female subjects of reproductive age must undergo a negative serum pregnancy test
within 3 days before the start of the study medication and be willing to use a
medically approved highly effective contraceptive measure (e.g., intrauterine
device, contraceptive pill, or condom) during the study and within 3 months after
the last administration of the study medication; Male subjects with a female partner
of reproductive age should be surgically sterilized or agree to use an effective
method of contraception during the study period and for 3 months after the last
study dose.
- Willing and able to follow the test and follow-up procedures.
- Be able to understand the nature of the trial and complete the signing of written
informed consent.
Exclusion Criteria:
- Only ALK positive or TP53 mutation;
- Patients who have received any previous ALK-TKI treatment;
- Subjects with known EGFR mutations which are sensitive to available targeted
inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21
[L858R] substitution mutations) are excluded. All subjects with non-squamous
histology must have been tested locally for EGFR mutation status; use of an
FDA-approved test is strongly encouraged (EGFR mutation testing may be performed
during the Screening Period, Non-squamous subjects with unknown or indeterminate
EGFR status may not be included);
- Subjects with untreated CNS metastases are excluded;
- Subjects with previous malignancies (except non-melanoma skin cancers, and the
following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or
breast) are excluded unless a complete remission was achieved at least 2 years prior
to study entry and no additional therapy is required or anticipated to be required
during the study period;
- Active hepatitis B (serum HBV DNA≥1.0E+4 copies /ml[i.e. 2,000 IU/ml]), positive for
hepatitis C virus antibody, HIV antibody, and treponema pallidum antibody;
- Women of childbearing age who had a positive serum pregnancy test 7 days before the
start of treatment, women who were pregnant or lactating, or male and female
subjects who did not take effective contraceptive measures or planned to have
children during the whole treatment period and 3 months after the end of treatment;
- Patients who have used any of the following drugs within 14 days before the first
dose or need to combine them during treatment: drugs at risk for prolonged QTc
and/or torsive-tip ventricular tachycardia; CYP3A strong inhibitor or strong
inducer;
- Major surgery or immunotherapy was performed within 4 weeks before the first dose;
He received radiotherapy within 2 weeks before the first dose.
- Imaging (CT or MRI) showed that the tumor invaded the great blood vessels or it was
judged that the tumor was very likely to invade the important blood vessels and
cause fatal massive bleeding during the subsequent study
- Previous interstitial lung disease, drug-induced interstitial disease, or any
clinically documented active interstitial lung disease; CT scan at baseline revealed
the presence of idiopathic pulmonary fibrosis
- Other severe, acute, or chronic medical conditions, including uncontrolled diabetes
or medical or psychiatric disorders or laboratory abnormalities, that, in the
opinion of the investigator, may increase the risk associated with study
participation or may interfere with the interpretation of the study results;
- Other circumstances deemed inappropriate by the investigator for participation in
the trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-Sen University Cancer Center
Address:
City:
Guangzhou
Country:
China
Start date:
August 1, 2022
Completion date:
December 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
First Affiliated Hospital of Wenzhou Medical University
Agency class:
Other
Collaborator:
Agency:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Collaborator:
Agency:
Shenyang Chest Hospital
Agency class:
Other
Collaborator:
Agency:
Hebei Medical University Fourth Hospital
Agency class:
Other
Collaborator:
Agency:
First People's Hospital of Foshan
Agency class:
Other
Collaborator:
Agency:
Fifth Affiliated Hospital, Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Guangzhou Institute of Respiratory Disease
Agency class:
Other
Collaborator:
Agency:
Central People's Hospital of Zhanjiang
Agency class:
Other
Collaborator:
Agency:
Guangdong Provincial Agricultural Reclamation Central Hospital
Agency class:
Other
Collaborator:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Collaborator:
Agency:
West China Hospital
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Collaborator:
Agency:
Yuebei People's Hospital
Agency class:
Other
Collaborator:
Agency:
Yunnan Cancer Hospital
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05491811
