Ensartinib in Combination With Bevacizumab in ALK-positive NSCLC Patients With TP53 Mutation
- Conditions
- Non-Small Cell Lung Cancer
- Registration Number
- NCT05491811
- Lead Sponsor
- Sun Yat-sen University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 49
Inclusion Criteria:<br><br> - Histologically or cytologically confirmed advanced (stage IIIB) or metastatic (stage<br> IV) NSCLC;<br><br> - ALK positive with TP53 mutation was confirmed by tissue samples or blood in each<br> center; TP53 mutation detection needs to be confirmed by NGS. ALK positive can be<br> detected by NGS,IHC,RT-PCR and FISH;<br><br> - Age = 18 years old;<br><br> - ALK-TKI-naive patients, and allowed to have received at most one line previous<br> chemotherapy;<br><br> - ECOG Performance status (PS) score is 0-2;<br><br> - Karnofsky Performance Status of =70;<br><br> - Subjects with CNS metastases are only eligible if the CNS metastases are adequately<br> treated with radiotherapy and/or surgery and subjects are neurologically returned to<br> baseline (except for residual signs or symptoms related to the CNS treatment) for at<br> least 1 week prior to randomization.<br><br>A.Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3<br>weeks for neurological stabilization before randomization.<br><br>B.This exception does not include carcinomatous meningitis which is excluded regardless<br>of clinical stability.<br><br> - Life expectancy of at least 12 weeks;<br><br> - Able to swallow oral drugs;<br><br> - It has certain organ system functions, defined as follows:<br><br>A. Absolute neutrophil count (ANC) =1.5 x 109/L B. Platelets =100 x 109/L C. hemoglobin<br>=9 g per deciliter (=90g per liter) note that blood transfusions are permitted to achieve<br>the required hemoglobin level.<br><br>D. Total bilirubin =1.5 times upper limit of normal (ULN) E. In the absence of liver<br>metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5×ULN;<br>In case of liver metastasis, =5×ULN.<br><br>F. Creatinine =1.5 x ULN. If = 1.5 × ULN and creatinine clearance value calculated by<br>Cockcroft-Gault method = 50 mL/min (0.83 mL/s), patients were still eligible for<br>inclusion.<br><br> - Female subjects of reproductive age must undergo a negative serum pregnancy test<br> within 3 days before the start of the study medication and be willing to use a<br> medically approved highly effective contraceptive measure (e.g., intrauterine<br> device, contraceptive pill, or condom) during the study and within 3 months after<br> the last administration of the study medication; Male subjects with a female partner<br> of reproductive age should be surgically sterilized or agree to use an effective<br> method of contraception during the study period and for 3 months after the last<br> study dose.<br><br> - Willing and able to follow the test and follow-up procedures.<br><br> - Be able to understand the nature of the trial and complete the signing of written<br> informed consent.<br><br>Exclusion Criteria:<br><br> - Only ALK positive or TP53 mutation;<br><br> - Patients who have received any previous ALK-TKI treatment;<br><br> - Subjects with known EGFR mutations which are sensitive to available targeted<br> inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21<br> [L858R] substitution mutations) are excluded. All subjects with non-squamous<br> histology must have been tested locally for EGFR mutation status; use of an<br> FDA-approved test is strongly encouraged (EGFR mutation testing may be performed<br> during the Screening Period, Non-squamous subjects with unknown or indeterminate<br> EGFR status may not be included);<br><br> - Subjects with untreated CNS metastases are excluded;<br><br> - Subjects with previous malignancies (except non-melanoma skin cancers, and the<br> following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or<br> breast) are excluded unless a complete remission was achieved at least 2 years prior<br> to study entry and no additional therapy is required or anticipated to be required<br> during the study period;<br><br> - Active hepatitis B (serum HBV DNA=1.0E+4 copies /ml[i.e. 2,000 IU/ml]), positive for<br> hepatitis C virus antibody, HIV antibody, and treponema pallidum antibody;<br><br> - Women of childbearing age who had a positive serum pregnancy test 7 days before the<br> start of treatment, women who were pregnant or lactating, or male and female<br> subjects who did not take effective contraceptive measures or planned to have<br> children during the whole treatment period and 3 months after the end of treatment;<br><br> - Patients who have used any of the following drugs within 14 days before the first<br> dose or need to combine them during treatment: drugs at risk for prolonged QTc<br> and/or torsive-tip ventricular tachycardia; CYP3A strong inhibitor or strong<br> inducer;<br><br> - Major surgery or immunotherapy was performed within 4 weeks before the first dose;<br> He received radiotherapy within 2 weeks before the first dose.<br><br> - Imaging (CT or MRI) showed that the tumor invaded the great blood vessels or it was<br> judged that the tumor was very likely to invade the important blood vessels and<br> cause fatal massive bleeding during the subsequent study<br><br> - Previous interstitial lung disease, drug-induced interstitial disease, or any<br> clinically documented active interstitial lung disease; CT scan at baseline revealed<br> the presence of idiopathic pulmonary fibrosis<br><br> - Other severe, acute, or chronic medical conditions, including uncontrolled diabetes<br> or medical or psychiatric disorders or laboratory abnormalities, that, in the<br> opinion of the investigator, may increase the risk associated with study<br> participation or may interfere with the interpretation of the study results;<br><br> - Other circumstances deemed inappropriate by the investigator for participation in<br> the trial.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 12-month Progression-free Survival (PFS) rate
- Secondary Outcome Measures
Name Time Method PFS;Objective Response Rate (ORR);Duration of Response (DoR);Disease Control Rate (DCR);Overall Survival (OS);Disease-related symptom improvement