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

NCT02691299 | Completed Phase 3 DMC

• 1 other identifier: 2015-013-00CH1
• Study Type: interventional
• Target: 527
• Locations: 1 country
• Sites: 11

Brief Summary

Fruquintinib/Placebo 5 mg, QD, orally administered under fasting conditions for 3 consecutive weeks followed by one-week off to evaluate the survival benefit of patients with advanced non-squamous NSCLC treated with Fruquintinib.

Conditions

NSCLC

Keywords

NSCLC

Outcome Measures

Primary Outcomes (1)

• overall survival (OS)

  Duration from randomization to death from any cause

  From the date of randomization until the date of death from any cause, Assessed up to 15 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 12 months

• progression free survival (PFS)

  From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 12 months

• Disease Control Rate (DCR)

  From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 12 months

• duration of response (DOR)

  From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 12 months

• safety and tolerability by incidence, severity and outcome of adverse events

  From randomization to 30 days after last dose, assessed up to 13 months

Study Arms (2)

Treatment Arm

ACTIVE COMPARATOR

All subjects will receive study treatment in 4-week cycles: Fruquintinib, QD, 5mg with best supportive care for 3 consecutive weeks, and then one week off. Tumor assessment will be performed every 4 weeks in the first 2 cycles, and every 8 weeks since the 3rd cycle, until disease progression or death. Subsequent anti-neoplastic treatment and survival status will be followed up after disease progression.

Drug: Fruquintinib

Control Arm

PLACEBO COMPARATOR

All subjects will receive study treatment in 4-week cycles: Placebo, QD, 5mg with best supportive care for 3 consecutive weeks, and then one week off. Tumor assessment will be performed every 4 weeks in the first 2 cycles, and every 8 weeks since the 3rd cycle, until disease progression or death. Subsequent anti-neoplastic treatment and survival status will be followed up after disease

Drug: Placebo

Interventions

Fruquintinib DRUG

Fruquintinib is a capsule in the form of 5mg and 1mg, orally once daily. 3 weeks on/1 week off

Also known as: HMPL-013

Treatment Arm

Placebo DRUG

Placebo is a capsule in the form of 5mg and 1mg, orally once daily. 3 weeks on/1 week off

Also known as: HMPL-013 placebo

Control Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fully understand the study and sign the informed consent form voluntarily;
• Histologically or cytologically diagnosed with local advanced and/or metastatic stage IIIB/IV non-squamous NSCLC;
• Disease progressed or developed non-tolerable toxicity after 2 lines of systemic chemotherapy (not including TKI therapy); Notes: a. The first-line chemotherapy should be platinum-based doublets regimens; b. For each line of systemic therapy, at least one treatment cycle should be completed, and maintenance therapy using one of the doublets is considered as the same line of therapy; c. Previous adjuvant/neoadjuvant therapy is allowed. If disease progressed during the adjuvant/neoadjuvant therapy period or within 1 year after completion of the above treatment, it is considered that patient failed the first-line systemic chemotherapy;
• Patients with EGFR genetic test negative; or positive with EGFR, test result but resistant or intolerable to related targeted therapies;
• Patients with ALK test negative; or positive with ALK test result but resistant or intolerable to related targeted therapies;
• Aged 18-75 years (inclusive);
• Measurable disease (according to RECIST1.1);
• ECOG Performance Status score 0-1;
• Life expectancy \>12 weeks.

You may not qualify if:

• Patients who have participated in another clinical trial or received systemic anti-neoplastic therapy, radiotherapy or biotherapy within 3 weeks prior to administration of the study drug; or received EGFR-TKI treatment in the past 1 week.
• Patients who have previously received therapy with VEGFR inhibitors;
• Patients who have not recovered from toxicity caused by previous anti-neoplastic treatment (CTCAE \> grade 1), or not completely recovered from previous surgery;
• Patient with active brain metastasis (untreated with proper radiation therapy, showing clinical symptoms or symptom stable time less than 4 weeks, or indicated for symptomatic treatment for brain metastasis, etc.);
• Patients with other primary malignancies within the past 5 years except basal cell carcinoma of skin or carcinoma in situ of cervix;
• Patients with uncontrolled active infections, e.g. acute pneumonia, active hepatitis B or active hepatitis C, etc. (for patients with a history of hepatitis B, whether treated or not, HBV DNA ≥500copies or ≥ 100IU / ml);
• Patients with dysphagia or known drug malabsorption;
• Patients 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;
• Patients fulfilling any of the following criteria shall 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 aminotransferase \>2.5×ULN (according to reference range in each clinical study site); ALT and AST \> 5×ULN in patients with liver metastasis;
• \) Clinically significant electrolyte abnormality;
• \) Blood creatinine \> ULN and creatinine clearance \<60 ml/min;
• \) Urine protein 2+ or more, or 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 site);

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (11)

307 Hospital of PLA

Beijing, Beijing Municipality, 100071, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Beijing Chest Hospital

Beijing, Beijing Municipality, 101149, China

Location

Guangdong General Hospital

Guangzhou, Guangdong, 510080, China

Location

Nantong Tumor Hospital

Nantong, Jiangsu, 226000, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Linyi Tumor Hospital

Linyi, Shandong, 276001, China

Location

The Cancer Hospital of Fudan University

Shanghai, Shanghai Municipality, 200000, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

West China Hospital

Chengdu, Sichuan, 610041, China

Location

The First Affiliated Hosptial of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Interventions

HMPL-013

Study Officials

• Songhua Fan, M.D.

  HMP MediPharma Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2016
• First Posted: February 25, 2016
• Study Start: December 9, 2015
• Primary Completion: September 21, 2018
• Study Completion: November 16, 2018
• Last Updated: February 12, 2019

Record last verified: 2019-02

Locations

CN (11)