Non-small Cell Lung Cancer, RET Fusion, Pralsetinib
Conditions
Brief summary
This study is a single-arm, multicenter real-world clinical study designed to evaluate the safety and efficacy of Leucogen (a leukocyte-increasing agent) as a prophylactic treatment in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who are being treated with Pralsetinib.
Interventions
DRUGPralsetinib
Pralsetinib 400mg orally once daily on an empty stomach (4 weeks as a cycle, until disease progression, death, or intolerance)
DRUGLeucogen
Leucogen 20mg orally three times daily for continuous prophylactic treatment for 3 months
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* (1)Aged ≥ 18 years, male or female; * (2)Treatment-naive patients with histopathologically confirmed locally advanced or metastatic lung adenocarcinoma that is unresectable and not eligible for curative radiotherapy; * (3)RET fusion-positive; * (4)Subjects with locally advanced (determined by the investigator as unsuitable for surgery or radiotherapy) or metastatic NSCLC who have not received any systemic anti-tumor treatment; * (5)Laboratory tests indicating adequate organ function in subjects, including:a. Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; Platelet Count (PLT) ≥ 100×10⁹/L; Hemoglobin (HGB) ≥ 90g/L;b. Without liver metastasis, AST and ALT ≤ 3× upper limit of normal (ULN); with liver metastasis, AST and ALT ≤ 5× ULN;c. Serum Total Bilirubin (TBIL) ≤ 1.5× ULN; for patients with Gilbert's syndrome, TBIL ≤ 3× ULN is allowed;d. Creatinine Clearance (CrCL) ≥ 40 ml/min (calculated by the Cockcroft-Gault formula); * (6)ECOG Performance Status score of 0-2 at screening, with no significant disease progression within 2 weeks before screening; * (7)Expected survival \> 12 weeks after the first dose; * (8) Reproductive-aged female subjects are not pregnant and have no plans for pregnancy. Both reproductive-aged female and male subjects agree to use effective contraceptive measures during the study and within 6 months after drug discontinuation; * (9) Understand and voluntarily participate in the study, and sign the informed consent form.）
Exclusion criteria
* (1) Histological or cytological examination indicates squamous cell-predominant non-small cell lung cancer (NSCLC), small cell lung cancer, neuroendocrine carcinoma, or other similar malignancies; * (2) Having received the following treatments:a. Major surgery performed within 4 weeks before the first dose or planned to be performed during the trial, excluding procedures such as vascular access establishment, mediastinoscopy, or thoracoscopy-guided biopsy;b. Use of strong CYP3A4 inhibitors within 7 days before the first dose or strong CYP3A4 inducers within 21 days before the first dose; use of traditional Chinese medicines (TCMs) or TCM preparations indicated for anti-tumor therapy, or TCMs/TCM preparations with adjuvant anti-tumor effects within 2 weeks before the first dose or expected to be used during the trial; * (3) Patients with spinal cord compression or symptomatic leptomeningeal metastasis; * (4) Patients with symptomatic and unstable pleural effusion or ascites; those whose clinical symptoms are stable for at least 14 days after thoracentesis or paracentesis may be enrolled; * (5) History of other malignant tumors or current concurrent other malignant tumors (excluding malignant tumors that have been cured by radical surgery and recurrence-free for 5 years, such as carcinoma in situ of the cervix, basal cell carcinoma of the skin, and papillary thyroid carcinoma); * (6) Past history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment; or clinical manifestations suggestive of interstitial lung disease; * (7) Having severe or uncontrolled systemic diseases requiring treatment, which the investigator deems unsuitable for trial participation, including hypertension, diabetes mellitus, chronic heart failure (NYHA cardiac function classification III-IV), unstable angina pectoris, myocardial infarction within 1 year, active hemorrhage, and other diseases; * (8) Resting QT interval (QTc) \> 470 msec detected by clinical electrocardiogram (ECG) screening; * (9) Clinically significant QT interval prolongation or other arrhythmias or clinical conditions that the investigator believes may increase the risk of QT interval prolongation, such as complete left bundle branch block, third-degree atrioventricular block, congenital long QT syndrome, severe hypokalemia, or concurrent use of drugs that may prolong the QT interval; * (10) Severe gastrointestinal dysfunction or other diseases that may affect the intake, transport, or absorption of study drugs; * (11) Patients with infectious diseases requiring intravenous medication; * (12) Known or suspected allergy to Pralsetinib or other components of its preparation; * (13) Female subjects who are pregnant, lactating, or planning to become pregnant during the study, or female spouses of male subjects planning to become pregnant during the study; * (14) Subjects with poor compliance who cannot adhere to the study procedures, restrictions, or requirements; * (15) Other conditions that the investigator deems unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The grade and incidence of leukopenia and neutropenia at 1 month after the first administration of Pralsetinib | up to 24 months | Metric/method of measurement:Blood samples are collected at specified time points, and indicator values are obtained through routine blood tests. The results are graded according to the CTCAE 5.0 criteria, and finally the incidence of each grade is calculated. At 1 month after the first administration of Pralsetinib. Assessed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The grade and incidence of Leukopenia and neutropenia at 2 months and 3 months after the first administration of Pralsetinib | up to 24 months | Metric/method of measurement:Blood samples are collected at specified time points, and indicator values are obtained through routine blood tests. The results are graded according to the CTCAE 5.0 criteria, and finally the incidence of each grade is calculated. At 2 months and 3 months after the first administration of Pralsetinib. |
| Incidence of Grade 3 Treatment-Related Adverse Events (TRAE), and Incidence of Dose Interruption/Reduction/Disc continuation | up to 24 months | The incidence of Grade 3 Treatment-Related Adverse Events (TRAE) refers to the probability of recording treatment-related adverse events that meet the Grade 3 criteria of CTCAE Version 5.0 in subjects from the first administration to 28 days after the last administration, while the incidence of dose interruption/reduction/discontinuation refers to the probability of recording corresponding events caused by drug toxicity. |
| Time to Treatment Failure (TTF) | up to 24 months | Time from the start of treatment to the first occurrence of a treatment failure event |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 Items (EORTC QLQ-LC30) | Up to 24 months | EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Negative change from baseline scores indicates less symptom severity, and thus improvement on health status. |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | up to 24 months | QLQ-C30 has 30 questions and scores range from 0-100 after a linear transformation. Positive change from baseline scores on the GHS/QoL and functioning scales indicate improvement on health status/function, and negative change scores on symptom scales/items represent less symptom severity/improvement on symptom status. |
Contacts
CONTACTJialei Wang, MD
CONTACTHui Yu, MD
Outcome results
None listed