Advanced ALK-Positive or ROS1-Positive Non-Small Cell Lung Cancer
Conditions
Interventions
dose1:5mg
dose2:10mg
dose3:20mg
dose4:40mg
dose5:60mg
dose6:90mg
dose7:120mg
dose expansion:RF-A089
Sponsors
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Participants with histologically or cytologically confirmed, locally advanced or metastatic NSCLC with ALK- positive or ROS1- positive. ALK- positive Participants confirmed by fluorescence in situ hybridization(FISH), real-time fluorescent quantitative PCR(RT-PCR) or immunohistochemical (IHC), are unamenable or intolerable to at least one previous treatment with other ALK inhibitors, or can not use ALK inhibitors previously with various causes in dose escalation stage. And participants, who are unamenable or intolerable to chemotherapy, are also included in dose expansion stage. Participants with ROS1- positive confirmed by FISH or RT-PCR, are unamenable or intolerable to crizotinib or other ALK inhibitors or first-line chemotherapy; 2. measurable lesion: At least one measurable lesion as defined by RECIST version 1.1; Note: previous radiotherapy cannot be used as a measurable lesion unless there is clear progression; 3. Female or male, 18 years of age or older; 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 5. Life expectancy =12 weeks; 6. Confirming the following laboratory test results: (1) haematological indexes: Absolute neutrophil count=1.5×l0^9/L, Platelets =75×10^9/L, Hemoglobin =90g/L; (2) Adequate liver function: Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) = 2.5 x upper limit of normal (ULN) or AST and ALT = 5 x ULN if liver function abnormalities are due to underlying malignancy; alkaline phosphatase(ALP) = 2.5 x ULN; total serum bilirubin = 1.5 x ULN; (3) Adequate renal function: creatinine clearance=50ml/min calculated by Cockcroft-Gault formula; (4) Serum amylase= 1 x ULN, serolipase= 1 x ULN; 7. Participants must have recovered from treatment toxicities to = Grade 1 or to their pretreatment levels. (except for alopecia and vitiligo; neuropathy induced by previous anticancer therapy is stable or = Grade 2); 8. patients with brain metastases must meet the following conditions: no clinical symptoms associated with brain metastasis, and no systemic corticosteroid / anticonvulsant therapy; progression-free in patients with brain metastasis after 28 days of treatment; no risk of intracerebral hemorrhage; 9. Female and male patients with childbearing potential must agree to use an effective form of contraception throughout the whole study and within 180 days after the last dose; 10. Ability to understand trials and willingness to sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Interstitial pulmonary disease or interstitial pneumonia; 2. Participants with gastrointestinal symptoms such as nausea, vomiting and diarrhea, and the Grade is greater than 1 (CTCAE, version 5.0); 3. Participants with dysphagia, gastrointestinal dysfunction or gastrointestinal disease, which may significantly affect drug absorption; 4. Acute or chronic infectious diseases: active infection with hepatitis A, hepatitis B, or hepatitis C; HIV positivity; Treponema pallidum antibody positivity; 5. Administration of agents with potential QT interval prolonging effects, or ventricular tachycardia, strong/potent cytochrome P450 3A4 (CYP3A4) or P450 2C8 (CYP2C8) inhibitors or inducers within 14 days prior to the first administration of study drug and during the whole study; 6. Any previous (in the past 3 years) or concomitant malignancy except for tumors that were cured and did not recur within 3 years prior to enrollment, or completely removed basal cell carcinoma or squamous cell skin cancer, or any type of carcinoma in situ); 7. Impairment in cardiac function or clinically significant heart disease within 6 months prior to enrolment, including cardio-cerebrovascular accident/ apoplexy, transient cerebral ischemia, myocardial infarction, Poorly controlled hypertension (systolic > 160 mm Hg and/or diastolic > 100 mm Hg), severe/unstable angina pectoris, congestive heart failure (> grade II according to NYHA), coronary/peripheral artery bypass grafting; severe arrhythmia requiring specific treatment, including QTc > 450 ms or pacemaker implantation; 8. Uncorrectable hypokalemia; 9. History of eye diseases including but not limited to cornea, conjunctiva, fundus or lens; 10. Treatments prior to the first administration of test drug: (1) Participation in an investigational drug within 4 weeks or 5 half-lives (whichever time is longer); (2) major surgical intervention, chemotherapy or immunotherapy within 4 weeks; radiotherapy or anticancer Chinese medicine within 2 weeks; 11. History of alcohol/drug dependence; 12. Medical history of neurological or mental disorders, for example epilepsy; participants who have poor compliance. 13. Fertility women with positive pregnancy test , pregnant or lactating women; 14. According to the investigators' judgement, participants are not suitable for the trial with other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicities (DLTs) and percentage of DLTs in each dosage level;Adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| The Pharmacokinetics of RF-A089 in patients With Advanced Non-Small Cell Lung Cancer (NSCLC);objective response rate(ORR);best overall response rate(BOR);disease control rate(DCR);duration of response(DOR);Progression-Free Survival(PFS); | — |
Countries
China
Contacts
Public ContactYuankai SHI
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed