Clinical trial NCT03223376: A Phase III Study of Fruquintinib in Combination With Paclitaxel in Second Line Gastric Cancer(FRUTIGA)
Official title: A Phase III Study to Evaluate the Efficacy and Safety of Fruquintinib in Combination With Paclitaxel Versus Paclitaxel Alone in Second Line Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Advanced Gastric Cancer
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: Sun Yat-sen University
First posted: 2017-07-21
Enrollment: 703
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Fruquintinib once daily in 4 weeks treatment cycle (three weeks on and one week off) in combination with Paclitaxel 80mg/㎡（day1, 8, 15 of 4 weeks cycle) was well tolerated and demonstrated encouraging preliminary clinical antitumor activity in patients with advanced GC in ph1b/2 study. This study is aimed to evaluate the efficacy and safety of Fruquintinib in combination with Paclitaxel in the treatment of patients with aGC who have progressed after first line standard chemotherapy.

Detailed description: This is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial to compare the efficacy and safety of Fruquintinib combined with Paclitaxel versus Paclitaxel alone in patients with advanced gastric cancer who have progressed after first-line standard chemotherapy. After checking eligibility criteria, subjects will be randomized into Fruquintinib combined with Paclitaxel group (treatment group) or placebo combined with Paclitaxel group (control group) in a ratio of 1:1. Primary Efficacy Endpoint: Overall Survival (OS), Progression free survival (PFS) (According to RECIST Version 1.1). Secondary Efficacy Endpoints: Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DOR), EORTC QLQ-C30 (V3) .Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.03.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma
* Metastatic disease or locally advanced, unresectable disease
* Disease progression during or within 4 months after the last dose of the first-line therapy (with platinum/fluoropyrimidine )
* Adequate hepatic, renal, heart, and hematologic functions
* At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure
* Good performance status Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1

Exclusion Criteria:

* Pregnant or lactating women
* Any factors that influence the usage of oral administration
* Evidence of CNS metastasis
* Intercurrence with one of the following: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure
* Abuse of alcohol or drugs
* Less than 4 weeks from the last clinical trial
* Previous treatment with VEGFR inhibition
* Disability of serious uncontrolled intercurrence infection
* Proteinuria ≥ 2+ (1.0g/24hr)
* Have evidence or a history of bleeding tendency within two months of the enrollment randomization, regardless of seriousness
* Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc.
* Within 6 months before the first treatment occurs acute myocardial infarction, acute coronary syndrome or CABG
* Bone fracture or wounds that was not cured for a long time
* Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant Therapy
* The tumor invades a large vessel structure, such as the pulmonary artery, superior vena cava, or inferior vena cava

Primary outcomes:
measure: Overall survival (OS)
timeFrame: from randomization until death due to any cause, assessed up to 3 year
measure: Progression free survival (PFS)
timeFrame: from the date of randomization to the date of the first documented progressive disease or date of death due to any cause, assessed up to 1 year]
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
measure: Disease control rate (DCR)
timeFrame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
measure: Safety and tolerance evaluated by incidence, severity and outcomes of AEs
timeFrame: from first dose to 30 days post the last dose
measure: Duration of response, DOR
timeFrame: : From the first documented PR or CR until the first documented PD or death，assessed up to 2 years
measure: The European Organization for Reasearch and Treatment of Cancer（EORTC ） Quality of Life Questionnaire-Core 30 V3.0 (QLQ-C30 v3.0)
timeFrame: Evaluation before the beginning of each treatment cycle, at the end of treatment, and at the 30 days post the last dose，up to 2 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: Hutchison Medi Pharma Invesigational sites
state: Anhui
city: Guangzhou
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Guangdong
city: Harbin
country: China
facility: Hutchison Medi Pharma Investigational site
state: Heilongjiang
city: Nanjing
country: China
facility: Huchison Medi Pharma Investigational site
state: Jiangsu
city: Hangzhou
country: China
facility: Hutchison Medi Pharma Investigational sites
state: Zhejiang
city: Beijing
country: China
facility: Hutchison Medi Pharma Investigational sites
city: Shanghai
country: China
facility: Hutchison Medi Pharma Investigational site
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu, MD
role: PRINCIPAL_INVESTIGATOR
References: