A Clinical Trial of Fruquintinib in Patients With Advanced Non-small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02590965
• Other study ID #: 2014-013-00CH1
• Status: Completed
• Phase: Phase 2
• Start date: May 29, 2014
• Est. completion date: February 10, 2017

Study information

• Verified date: February 2020
• Source: Hutchison Medipharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: February 10, 2017
• Est. primary completion date: August 7, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Fruquintinib
After checking eligibility criteria, subjects will be randomized into Fruquintinib plus best supportive care group (treatment group) or placebo plus best supportive care group (control group) in a ration of 2:1.
• Placebo
Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/1 week off

Locations

Country	Name	City	State
China	307 Hospital of PLA	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chest Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	West China Hospital	Chengdu	Sichuan
China	Xi Nan Hospital, Third Military Medical University	Chongqing	Chongqing
China	Guangdong General Hospital	Guangzhou	Guangdong
China	The First Affiliated Hosptial of College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Linyi Tumor Hospital	Linyi	Shandong
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	The Cancer Hospital of Fudan University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited	Shanghai Chest Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progressive free survival (PFS)	To compare the Progressive Free Survival (PFS) of Fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients advanced non-squamous NSCLC patients who failed to standard second-line chemotherapy according to RECIST 1.1	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	Objective response rate (ORR)	To evaluate objective response rate (ORR) in the two groups according to RECIST 1.1	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	Disease control rate (DCR)	To evaluate disease control rate (DCR) in the two groups according to RECIST 1.1	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	Overall survival (OS)	To evaluate overall survival (OS) in the two groups	every 2 months from randomization to death, assessed up to one year
Secondary	safety and tolerability by incidence, severity and outcome of adverse events	To evaluate the safety and tolerability in the two groups by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.	From randomization to 30 days after last dose