Clinical trial NCT02590965: A Clinical Trial of Fruquintinib in Patients With Advanced Non-small Cell Lung Cancer
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center Phase II Clinical Trial to Evaluate the Efficacy and Safety of Fruquintinib Plus Best Supportive Care in Patients With Advanced Non-squamous Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Chest Hospital
First posted: 2015-10-29
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled, multi-center Phase II clinical trial to evaluate the efficacy and safety of Fruquintinib plus best supportive care in patients with advanced non-squamous non-small cell lung cancer who failed to second-line standard chemotherapy.

Detailed description: Approximately 90 subjects will be randomized to Fruquintinib plus best supportive care or placebo plus best supportive care at a 2:1 ratio.

Randomization will be stratified by EGFR (epidermal growth factor receptor) gene status: mutant vs. wild type vs. unknown.

All subjects will receive Fruquintinib/placebo for consecutive 3 weeks, followed by one-week rest. A treatment cycle consists of 4 weeks. Tumor assessment will be performed every 4 weeks in the first 3 cycles, and every 8 weeks since the 4th cycle, until disease progression. Further treatment and survival follow-up after progression will be recorded.

Eligibility criteria: Inclusion Criteria:

1. Fully understand the study and sign the informed consent form voluntarily;
2. Histologically and/or cytologically diagnosed with local advanced and/or metastatic stage IIIB/IV non-squamous NSCLC;
3. Previously failed to two chemotherapy regimens(treatment failure is defined as disease progression or intolerable toxicity), patients with positive EGFR mutation permitted to treated by EGFR-TKI previously; patients with EGFR wild type or unknown whether or not treated by EGFR-TKI previously;
4. Aged 18-75 years (inclusive);
5. Body weight ≥40 kg;
6. Evident measurable lesion(s) (according to RECIST1.1);
7. ECOG Performance Status 0-1;
8. Expected survival \>12 weeks

Exclusion Criteria:

1. Treatment in another clinical trials in the past 3 weeks; or treatment with systemic anti-tumor chemotherapy, radiotherapy or biotherapy within 3 weeks prior to administration of the study drug;
2. Previous therapy with VEGF/VEGFR inhibitors;
3. Unrecovered from toxicity caused by previous anti-cancer treatment (CTCAE \>grade 1), or not completely recovered from previous surgery;
4. Previous active brain metastasis (without radiotherapy previously, or symptoms stable \< 4 weeks, or with clinical symptoms, or with medication to control symptoms);
5. Other malignancies except basal cell carcinoma or cervical carcinoma in situ in the past 5 years;
6. Uncontrolled clinical active infection, e.g. acute pneumonia and active hepatitis B;
7. Dysphagia or known drug malabsorption;
8. Present active duodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases or other conditions that may lead to gastrointestinal bleeding or perforation according to the investigators' judgment; or with a history of intestinal perforation or intestinal fistula;
9. Have evidence or a history of thrombosis or bleeding tendency, regardless of seriousness;
10. Stroke and/or transient ischemic attack within 12 months prior to enrollment;
11. Appropriate organ function. Patients with any of the following conditions will be excluded:

    * Absolute neutrophil count (ANC) \<1.5×109/L, platelet \<100×109/L or hemoglobin \<9 g/dL within 1 week prior to enrollment;
    * Serum total bilirubin \>1.5 upper limit of normal (ULN), alanine transaminase and aspartate transferase \>1.5×ULN; ALT and AST \> 3×ULN in patients with liver metastasis;
    * Electrolyte abnormality of clinical significance;
    * Blood creatinine \>ULN and creatinine clearance \<60 ml/min;
    * Urine protein 2+ or above, or 24 h urine protein quantification ≥1.0 g/24 h;
    * Activated partial thromboplastin time (APTT) or/and INR and prothrombin time (PT) \>1.5×ULN (according to reference range in each clinical study center);
12. Uncontrolled hypertension, systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg with medication; or heart failure NYHA classification ≥ grade 2;
13. Heart function evaluation: left ventricular ejection fraction \<50% (echocardiography);
14. Acute myocardial infarction, severe/unstable angina or coronary bypass surgery within 6 months prior to enrollment; history of arterial thrombosis or deep venous thrombosis;
15. Skin wound, surgical site, wound site, severe mucosal ulcer or fracture without complete healing;
16. Female subjects who are pregnant or lactating or of child bearing potential with positive pregnancy test result before the first dose;
17. Patients with child bearing potential who or whose sexual partners are not willing to take contraceptive measures;
18. Any clinical or laboratory abnormalities unfit to participate in this clinical trial according to the investigator's judgment;
19. Serious psychological or psychiatric disorders which may affect subject compliance in this clinical study;
20. Allergy to Fruquintinib and/or excipient contained in trial drugs.

Primary outcomes:
measure: Progressive free survival (PFS)
timeFrame: measured every 4 weeks at first 2 cycles and every 8 weeks since the third cycle from randomization to disease progression, assessed up to one year
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: measured every 4 weeks at first 2 cycles and every 8 weeks since the third cycle from randomization to disease progression, assessed up to one year
measure: Disease control rate (DCR)
timeFrame: measured every 4 weeks at first 2 cycles and every 8 weeks since the third cycle from randomization to disease progression, assessed up to one year
measure: Overall survival (OS)
timeFrame: every 2 months from randomization to death, assessed up to one year
measure: safety and tolerability by incidence, severity and outcome of adverse events
timeFrame: From randomization to 30 days after last dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: 307 Hospital of PLA
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital
state: Beijing
city: Chongqing
country: China
facility: Xi Nan Hospital, Third Military Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Linyi
country: China
facility: Linyi Tumor Hospital
state: Shandong
city: Shanghai
country: China
facility: The Cancer Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hosptial of College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References:
citation: Lu S, Chang J, Liu X, Shi J, Lu Y, Li W, Yang JJ, Zhou J, Wang J, An T, Yang L, Liu Z, Zhou X, Chen M, Hua Y, Su W. Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Fruquintinib After Two Prior Chemotherapy Regimens in Chinese Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Apr 20;36(12):1207-1217. doi: 10.1200/JCO.2017.76.7145. Epub 2018 Mar 12.