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

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ClinicalTrials.gov Identifier: NCT02590965
Recruitment Status : Completed
First Posted : October 29, 2015
Last Update Posted : February 23, 2018
Sponsor:
Collaborator:
Shanghai Chest Hospital
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE March 26, 2015
First Posted Date  ICMJE October 29, 2015
Last Update Posted Date February 23, 2018
Actual Study Start Date  ICMJE May 29, 2014
Actual Primary Completion Date August 7, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2015)
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 ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02590965 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2015)
  • 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 ]
    To evaluate objective response rate (ORR) in the two groups according to RECIST 1.1
  • 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 ]
    To evaluate disease control rate (DCR) in the two groups according to RECIST 1.1
  • Overall survival (OS) [ Time Frame: every 2 months from randomization to death, assessed up to one year ]
    To evaluate overall survival (OS) in the two groups
  • safety and tolerability by incidence, severity and outcome of adverse events [ Time Frame: From randomization to 30 days after last dose ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial of Fruquintinib in Patients With Advanced Non-small Cell Lung Cancer
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • 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 Name: HMPL-013
  • Drug: Placebo
    Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/1 week off
    Other Name: HMPL-013-placebo
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 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
    Intervention: Drug: Fruquintinib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 28, 2015)
91
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 10, 2017
Actual Primary Completion Date August 7, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02590965
Other Study ID Numbers  ICMJE 2014-013-00CH1
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE Shanghai Chest Hospital
Investigators  ICMJE
Study Director: Ye Hua, MD Huchison Medipharma Limited
PRS Account Hutchison Medipharma Limited
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP