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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Fruquintinib

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.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100071
      • 307 Hospital of PLA
    • Beijing, Beijing, China, 101149
      • Beijing Chest Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • Xi Nan Hospital, Third Military Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
  • Jiangsu
    • Nantong, Jiangsu, China, 226000
      • Nantong Tumor Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shandong
    • Linyi, Shandong, China, 276001
      • Linyi Tumor Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
    • Shanghai, Shanghai, China, 200000
      • The Cancer Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hosptial of College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Placebo is a capsule in the form of 1mg and 5 mg, orally, once daily, 3 weeks on/1week off with best supportive care.	Drug: Placebo; Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/1 week off; Other Names: HMPL-013-placebo
Experimental: Treatment Group; 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	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.; Other Names: HMPL-013

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Overall survival (OS)	To evaluate overall survival (OS) in the two groups	every 2 months from randomization to death, assessed up to one year
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

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Collaborators: Shanghai Chest Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2014
• Primary Completion (Actual): August 7, 2015
• Study Completion (Actual): February 10, 2017

Study Registration Dates

• First Submitted: March 26, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Actual): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

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
• Other Study ID Numbers: 2014-013-00CH1