A Study of Famitinib Plus Docetaxel in Patients With Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC)

Docetaxel Plus Famitinib Versus Docetaxel Plus Placebo in Patients With Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: famitinib L + docetaxel; Drug: famitinib M + docetaxel; Drug: famitinib H + docetaxel

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Famitinib + docetaxel; Low, medium and high dose of famitinib and 60 mg/m^2 docetaxel every 3 weeks	Drug: famitinib L + docetaxel; famitinib 15mg qd + docetaxel 60 mg/m^2; Drug: famitinib M + docetaxel; famitinib 20mg qd + docetaxel 60 mg/m^2; Drug: famitinib H + docetaxel; famitinib 25mg qd + docetaxel 60 mg/m^2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of famitinib in combination with standard-dose docetaxel(60 mg/m^2)	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)	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)		6 weeks
Incidences of Adverse Events according to Common Toxicity Criteria (CTC version 4.0) associated with increasing doses of famitinib		1 years
Pharmacokinetics-AUC	Area under the plasma concentration-time curve (AUC) for famitinib and docetaxel	6 weeks
Pharmacokinetics-Cmax	Maximum measured plasma concentration (Cmax) for famitinib and docetaxel	6 weeks
Pharmacokinetics-Tmax	Time from dosing to the maximum plasma concentration (Tmax) for famitinib and docetaxel	6 weeks
Pharmacokinetics-t1/2	Terminal half-life (t1/2(ss)) for famitinib and docetaxel	6 weeks
Progress free survival (PFS)		1 years

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: February 10, 2015
• First Posted (Estimate): February 18, 2015

Study Record Updates

• Last Update Posted (Actual): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: HR-FMTN- Ⅱ-NSCLC-COM