This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments fruquintinib, placebo
Phase phase 2
Target VEGF
Sponsor Hutchison Medipharma Limited
Collaborator Shanghai Chest Hospital
Start date April 2014
End date July 2016
Trial size 91 participants
Trial identifier NCT02590965, 2014-013-00CH1


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
(Placebo Comparator)
Placebo is a capsule in the form of 1mg and 5 mg, orally, once daily, 3 weeks on/1week off with best supportive care.
placebo HMPL-013-placebo
Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/1 week off
The subjects will receive oral Fruquintinib at fasting state 5mg+best supportive care, once daily for the first 3 consecutive weeks and dose holiday for 1 week according to their dose regimens until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent
fruquintinib HMPL-013
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.

Primary Outcomes

Progressive free survival (PFS)
time frame: 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

Objective response rate (ORR)
time frame: 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
Disease control rate (DCR)
time frame: 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
Overall survival (OS)
time frame: every 2 months from randomization to death, assessed up to one year
safety and tolerability by incidence, severity and outcome of adverse events
time frame: From randomization to 30 days after last dose

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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.

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Hutchison Medipharma Limited.