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

• ClinicalTrials.gov Identifier: NCT02590965
• Recruitment Status: Completed
• First Posted: October 29, 2015
• Last Update Posted: February 13, 2020
• Sponsor: Hutchison Medipharma Limited
• Collaborator: Shanghai Chest Hospital
• Information provided by (Responsible Party): Hutchmed ( Hutchison Medipharma Limited )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Fruquintinib; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 29, 2014
• Actual Primary Completion Date: August 7, 2015
• Actual Study Completion Date: February 10, 2017

Arms and Interventions

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 Name: 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 Name: HMPL-013

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

China, Beijing

307 Hospital of PLA

Beijing, Beijing, China, 100071

Beijing Cancer Hospital

Beijing, Beijing, China, 100142

Beijing Chest Hospital

Beijing, Beijing, China, 101149

China, Chongqing

Xi Nan Hospital, Third Military Medical University

Chongqing, Chongqing, China, 400038

China, Guangdong

Guangdong General Hospital

Guangzhou, Guangdong, China, 510080

China, Jiangsu

Nantong Tumor Hospital

Nantong, Jiangsu, China, 226000

China, Jilin

The First Hospital of Jilin University

Changchun, Jilin, China, 130021

China, Shandong

Linyi Tumor Hospital

Linyi, Shandong, China, 276001

China, Shanghai

The Cancer Hospital of Fudan University

Shanghai, Shanghai, China, 200000

Shanghai Chest Hospital

Shanghai, Shanghai, China, 200030

China, Sichuan

West China Hospital

Chengdu, Sichuan, China, 610041

China, Zhejiang

The First Affiliated Hosptial of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310003

Sponsors and Collaborators

Hutchison Medipharma Limited

Shanghai Chest Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hutchison Medipharma Limited
• ClinicalTrials.gov Identifier: NCT02590965
• Other Study ID Numbers: 2014-013-00CH1
• First Posted: October 29, 2015
• Last Update Posted: February 13, 2020
• Last Verified: February 2020

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms