Non-Small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
Famitinib is a tyrosin-inhibitor agent targeting at c-Kit, VEGFR2, PDGFR, VEGFR3, Flt1 and Flt3. Phase I study has shown that the toxicity is manageable. This study assessed the safety and maximum tolerated dose of continuous daily treatment with Famitinib plus docetaxel (60 mg/m\^2, every 3 weeks) in patients with Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC) to determine the recommended dose for the Phase II trial.
Interventions
DRUGfamitinib L + docetaxel
famitinib 15mg qd + docetaxel 60 mg/m\^2
DRUGfamitinib M + docetaxel
famitinib 20mg qd + docetaxel 60 mg/m\^2
DRUGfamitinib H + docetaxel
famitinib 25mg qd + docetaxel 60 mg/m\^2
Sponsors
Shanghai Pulmonary Hospital, Shanghai, China
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age:18-70 years; 2. ECOG PS (Eastern Cooperative Oncology Group Performance Status)of 0 or 1; 3. Life expectancy of at least 12 weeks; 4. Histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of stage IIIB or IV or recurrent NSCLC; 5. Relapse or failure of one first line prior platinum-based chemotherapy;EGFR mutation type previously treated with platinum-based chemotherapy and EGFR inhibitors; 6. At least one target tumour lesion that has not been irradiated within the past 3 months and that can accurately be measured ,according to RECIST 1.1; 7. Participants have adequate organ and marrow function as defined below: * Hemoglobin ≥ 90g/L ( no blood transfusion in 2 weeks) * Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L * Platelets(PLT)≥ 100×10\^9/L * Bilirubin \< 1.25×ULN(Upper Limit Of Normal) * ALT \< 2.5×ULN; ALT \< 5×ULN ( If have liver metastases) * AST \< 2.5×ULN; AST \< 5×ULN ( If have liver metastases) * Serum creatinine \< 1.25×ULN, and endogenous Cr clearance \> 45 ml/min(Cockcroft-Gault Formula) * Cholesterol ≤ 1.5×ULN and triglyceride≤ 2.5×ULN * Left ventricular ejection fraction(LVEF): ≥ LLN(Lower Limit Of Normal) by Color Doppler Ultrasonography 8. Female: Child bearing potential, a negative urine or serum pregnancy test result 7 days before initiating famitinib.All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article; 9. Patient has given written informed consent.
Exclusion criteria
1. More than one chemotherapy treatment regimen (except,either neoadjuvant or adjuvant or neoadjuvant plus adjuvant) for advanced and/or metastatic or recurrent NSCLC; 2. Previous therapy with other VEGFR inhibitors (including sunitinib,sorafenib,pazopanib,axitinib,other than bevacizumab) or docetaxel for treatment of NSCLC; 3. Radiographical evidence of cavitary or necrotic tumours; 4. Centrally located tumours with radiographical evidence (CT or MRI) of local invasion of major blood vessels; 5. Pre-existing ascites and/or clinically significant pleural effusion; 6. Pulmonary hemorrhage/ bleeding event ≥ CTCAE gr. 2 before initiating investigational drugs; 7. History of clinically significant haemoptysis within the past 3 months（24h \>half teaspoon）; 8. Current peripheral neuropathy greater than CTCAE grade 2; 9. Other malignancy within the past 3 years other than basal cell skin cancer, or carcinoma in situ of the cervix; 10. Active brain metastases (such as stable time ≤ 4 weeks,no radiotherapy treatment,any symptoms,or seizures treatment needing) or leptomeningeal disease.; 11. Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial; 12. Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy; 13. Treatment with cytotoxic drugs, radiotherapy(except extremities and brain) , immunotherapy , monoclonal antibody, or TKI inhibitor therapy within the past 4 weeks, being previous anti-cancer treatment interval ≤ 4 weeks.; 14. Patients with hypertension using combination therapy (systolic blood pressure\>140 mmHg, diastolic blood pressure\>90 mmHg). Patients with unstable angina, myocardial ischemia or myocardial infarction in the past 6 months, congestive heart failure\>NYHA II,and arrhythmia (including QTcF interval ≥ 450ms for male and 470ms for female); 15. Urine protein ≥ + + and confirmed the 24-hour urinary protein\>1.0 g; 16. History of major thrombotic or clinically relevant major bleeding event in the past 6 months，and known inherited predisposition to bleeding or thrombosis; 17. PT or APTT bias from normal range≥50%; 18. Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues;If the prothrombin time international normalized ratio (INR) ≤ 1.5, with the purpose of prevention, the use of small doses of warfarin (1mg orally, once daily) ， low-dose aspirin (less than 100mg daily) is allowed; 19. Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range; 20. Diabetes mellitus can not controlled with hypoglycemic agent; 21. Active or chronic hepatitis C and/or B infection with liver dysfunction; 22. History of immunodeficiency disease, concurrent acquired or congenital immunodeficiency,or history of organ transplantation; 23. Serious infections requiring systemic antibiotic therapy; 24. Variety of factors that affect the oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction); 25. Significant weight loss (\>10 %) within the past 6 months; 26. Pregnancy , breast feeding or child bearing potential, a positive urine or serum pregnancy test result 7 days before initiating famitinib; 27. Active alcohol or drug abuse; 28. Any contraindications for therapy with docetaxel；History of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80)；Hypersensitivity to famitinib and/or the excipients of the trial drugs；Hypersensitivity to contrast media; 29. Psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; 30. Patients unable to comply with the protocol; 31. Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of famitinib in combination with standard-dose docetaxel(60 mg/m^2) | 3 weeks | MTD was defined as the highest dose at which incidence of dose-limiting toxicities(DLTs) in Cyle 1 was ≤33.3%(0/3,1/6,2/6) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics-AUC | 6 weeks | Area under the plasma concentration-time curve (AUC) for famitinib and docetaxel |
| Pharmacokinetics-Cmax | 6 weeks | Maximum measured plasma concentration (Cmax) for famitinib and docetaxel |
| Pharmacokinetics-Tmax | 6 weeks | Time from dosing to the maximum plasma concentration (Tmax) for famitinib and docetaxel |
| Incidences of Adverse Events according to Common Toxicity Criteria (CTC version 4.0) associated with increasing doses of famitinib | 1 years | — |
| Objective Response Rate (ORR) | 6 weeks | — |
| Progress free survival (PFS) | 1 years | — |
| Pharmacokinetics-t1/2 | 6 weeks | Terminal half-life (t1/2(ss)) for famitinib and docetaxel |
Countries
China
Outcome results
None listed