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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04322539




Registration number
NCT04322539
Ethics application status
Date submitted
24/03/2020
Date registered
26/03/2020

Titles & IDs
Public title
A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer
Scientific title
A Global Multicenter Randomized Placebo-Controlled Phase 3 Trial To Compare The Efficacy And Safety Of Fruquintinib Plus Best Supportive Care To Placebo Plus Best Supportive Care In Patients With Refractory Metastatic Colorectal Cancer
Secondary ID [1] 0 0
2019-013-GLOB1
Universal Trial Number (UTN)
Trial acronym
FRESCO-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Metastatic Colon Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fruquintinib
Treatment: Drugs - Placebo

Experimental: Fruquintinib Plus Best Supportive Care (BSC) Group - Participants will be orally administered Fruquintinib 5 mg in combination with BSC once daily for 3 weeks of continuous dosing followed by a 1-week break (with each cycle length of 28 days).

Placebo comparator: Placebo Plus BSC Group - Participants will be orally administered Placebo 5 mg in combination with BSC once daily for 3 weeks of continuous dosing followed by a 1-week break (with each cycle length of 28 days).


Treatment: Drugs: Fruquintinib
Oral VEGFR inhibitor

Treatment: Drugs: Placebo
Placebo capsule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From date of randomization to death from any cause (up to 22 months)
Secondary outcome [1] 0 0
Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Timepoint [1] 0 0
From randomization until the first documentation of objective progression or death, whichever comes first (up to 22 months)
Secondary outcome [2] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [2] 0 0
From randomization until the first documentation of best overall response (up to 22 months)
Secondary outcome [3] 0 0
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [3] 0 0
From randomization until the first documentation of best overall response (up to 22 months)
Secondary outcome [4] 0 0
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [4] 0 0
From first occurrence of PR or CR until the first documentation progression or death, whichever comes first (up to 22 months
Secondary outcome [5] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [5] 0 0
From start of study drug administration up to 22 months
Secondary outcome [6] 0 0
Observed Plasma Concentrations of Fruquintinib and Metabolite M11
Timepoint [6] 0 0
Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 (Day 21): Predose and 2 hours, Cycle 3 (Day 1): Pre-dose, Cycle 3 (Day 21): Pre-dose and 2 hours, Cycle 5, 7, 9, 11, 13, 15 and 17 (Day 1): Pre-dose (Each cycle = 28 days)
Secondary outcome [7] 0 0
Change From Baseline of Electrocardiogram (ECG) Results - QTcF Intervals Using Fridericia's Formula
Timepoint [7] 0 0
Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days)
Secondary outcome [8] 0 0
Change From Baseline of ECG Results -QTcB Intervals Using Bazzett's Formula
Timepoint [8] 0 0
Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days)
Secondary outcome [9] 0 0
Correlation Between Fruquintinib Exposure-response With Efficacy (OS) and Safety (AEs) Endpoints
Timepoint [9] 0 0
Up to 42 months
Secondary outcome [10] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Scale Score
Timepoint [10] 0 0
Baseline, Cycle 2, 3 and 4 (Each cycle=28 days)
Secondary outcome [11] 0 0
Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score
Timepoint [11] 0 0
Baseline, Cycle 2, 3 and 4 (Each cycle=28 days)
Secondary outcome [12] 0 0
Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Health Utility Index Scores
Timepoint [12] 0 0
Baseline, Cycle 2, 3 and 4 (Each cycle=28 days)
Secondary outcome [13] 0 0
Health Care Resource Utilization: Duration of Hospital Visits by Participants
Timepoint [13] 0 0
From start of study drug administration up to 22 months
Secondary outcome [14] 0 0
Health Care Resource Utilization: Number of Participants With Any Concomitant Medications Prescribed
Timepoint [14] 0 0
From start of study drug administration up to 22 months

Eligibility
Key inclusion criteria
* Provide written informed consent;
* Age =18 years;
* Histologically and/or cytologically documented metastatic colorectal adenocarcinoma. RAS, BRAF, and microsatellite instability microsatellite instability (MSI)/mismatch repair (MMR) status for each patient must be documented, according to country level guidelines;
* Participants must have progressed on or been intolerant to treatment with either trifluridine/tipiracil (TAS-102) or regorafenib. Participants are considered intolerant to TAS-102 or regorafenib if they have received at least 1 dose of either agents and were discontinued from therapy for reasons other than disease progression. Participants who have been treated with both TAS-102 and regorafenib are permitted. Participants must also have been previously treated with standard approved therapies: fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and, if RAS wild-type, an anti-EGFR therapy;
* Participants with microsatellite-high (MSI-H) or mismatch repair deficient (dMMR) tumors must have been treated with immune checkpoint inhibitors if approved and available in the participant's country unless the patient is ineligible for treatment with a checkpoint inhibitor;
* Participants who received oxaliplatin in the adjuvant setting and developed metastatic disease during or within 6 months of completing adjuvant therapy are considered eligible without receiving oxaliplatin in the metastatic setting. Participants who developed metastatic disease more than 6 months after completion of oxaliplatin-containing adjuvant treatment must be treated with oxaliplatin-based therapy in the metastatic setting to be eligible;
* Body weight =40kg;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
* Have measurable disease according to RECIST Version 1.1, assessed locally. Tumors that were treated with radiotherapy are not measurable per RECIST Version 1.1, unless there has been documented progression of those lesions;
* Expected survival >12 weeks.
* For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form(s) of contraception, that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include: oral hormonal contraception (combined estrogen/ progestogen, or progestogen-only) associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or true sexual abstinence in line with the preferred and usual lifestyle of the participant. Highly effective contraception should always be combined with an additional barrier method (eg, diaphragm, with spermicide). The same criteria are applicable to male participants involved in this clinical trial if they have a partner of childbirth potential, and male participants must always use a condom.
* Participants with BRAF-mutant tumors must have been treated with a BRAF inhibitor if approved and available in the participant's home country unless the patient is ineligible for treatment with a BRAF inhibitor.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Absolute neutrophil count (ANC) <1.5×109/L, platelet count <100×109/L, or hemoglobin <9.0 g/dL. Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed;
* Serum total bilirubin >1.5 × the upper limit of normal (ULN). Participants with Gilbert syndrome, bilirubin <2 X ULN, and normal AST/ALT are eligible;
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × ULN in participants without hepatic metastases; ALT or AST >5 × ULN in participants with hepatic metastases;
* Serum creatinine >1.5 × ULN or creatinine clearance <60 mL/min. Creatinine clearance can either be measured in a 24-hour urine collection or estimated by the Cockroft-Gault equation.
* Urine dipstick protein =2+ or 24-hour urine protein =1.0 g/24-h. Participants with greater than 2+ proteinuria by dipstick must undergo a 24-hour urine collection to assess urine protein level;
* Uncontrolled hypertension, defined as: systolic blood pressure =140 mm Hg and/or diastolic blood pressure =90 mm Hg despite optimal medical management. Participants were required to have blood pressure values below both limits. Repeated assessments were permitted;
* International Normalized Ratio (INR) >1.5 x ULN or activated partial thromboplastin time (aPTT) >1.5 × ULN, unless the patient is currently receiving or intended to receive anticoagulants for prophylactic purposes;
* History of, or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation or fistulas; or any other condition that could, in the investigator's judgment, result in gastrointestinal hemorrhage or perforation; within the 6 months prior to screening;
* History or presence of hemorrhage from any other site (eg, hemoptysis or hematemesis) within 2 months prior to screening;
* History of a thromboembolic event, including deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial embolism within 6 months prior to screening.
* Stroke and/or transient ischemic attack within 12 months prior to screening;
* Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction (LVEF) <50% by echocardiogram;
* Mean corrected QT interval using the Fridericia method (QTcF) >480 msec or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in a first-degree relative.
* Concomitant medications with a known risk of causing QT prolongation and/or Torsades de Pointes.
* Systemic anti-neoplastic therapies (except for those described in Exclusion 18) or any investigational therapy within 4 weeks prior to the first dose of study drug, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and immunotherapy;
* Systemic small molecule targeted therapies (eg, tyrosine kinase inhibitors) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
* Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of study drug;
* Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the first dose of study drug.
* Use of strong inducers or inhibitors of CYP3A4 within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug;
* Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central venous catheter placement is allowed) within 60 days prior to the first dose of study drug or unhealed surgical incision;
* Any unresolved toxicities from a previous antitumor treatment greater than CTCAE v5.0 Grade 1 (except for alopecia or neurotoxicity grade=2);
* Known human immunodeficiency virus (HIV) infection;
* Known history of active viral hepatitis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Participants with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
* Clinically uncontrolled active infection requiring IV antibiotics;
* Tumor invasion of a large vascular structure, eg, pulmonary artery, superior or inferior vena cava;
* Women who are pregnant or lactating;
* Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease for 14 days or longer; participants requiring steroids within 4 weeks prior to start of study treatment are excluded;
* Other malignancy, except for non-melanoma skin cancer, in situ cervical ca or bladder ca (Tis and T1) that have been adequately treated during the 5 years prior to screening;
* Inability to take medication orally, dysphagia or an active gastric ulcer resulting from previous surgery (eg, gastric bypass) or a severe gastrointestinal disease, or any other condition that investigators believe may affect absorption of the investigational product;
* Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition (e.g., current alcohol or drug abuse) that investigators suspect may prohibit use of the investigational product, affect interpretation of study results, or put the patient at undue risk of harm based on the investigator's assessment;
* Known hypersensitivity to fruquintinib (or placebo) or any of its inactive ingredients including the azo dyes Tartrazine - FD&C Yellow 5 and Sunset yellow FCF - FD&C Yellow 6;
* Participants who have received prior fruquintinib;
* Live vaccine <28days before the first dose of study drug(s). Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2024
Actual
Sample size
Target
Accrual to date
Final
691
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Integrated Clinical Oncology Network Pty Ltd (Icon) - Brisbane
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Adelaide
Recruitment hospital [3] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [4] 0 0
Western Health - Melbourne
Recruitment hospital [5] 0 0
Austin Hopistal Medical Oncology Unit - Melbourne
Recruitment hospital [6] 0 0
Monash Health - Melbourne
Recruitment postcode(s) [1] 0 0
4001 - Brisbane
Recruitment postcode(s) [2] 0 0
5011 - Adelaide
Recruitment postcode(s) [3] 0 0
5042 - Adelaide
Recruitment postcode(s) [4] 0 0
3021 - Melbourne
Recruitment postcode(s) [5] 0 0
3084 - Melbourne
Recruitment postcode(s) [6] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Austria
State/province [24] 0 0
AUT
Country [25] 0 0
Belgium
State/province [25] 0 0
BEL
Country [26] 0 0
Belgium
State/province [26] 0 0
Wallonia
Country [27] 0 0
Czechia
State/province [27] 0 0
Moravia
Country [28] 0 0
Czechia
State/province [28] 0 0
Prague
Country [29] 0 0
Estonia
State/province [29] 0 0
Harju
Country [30] 0 0
Estonia
State/province [30] 0 0
Tartu
Country [31] 0 0
France
State/province [31] 0 0
Franche-Comte
Country [32] 0 0
France
State/province [32] 0 0
FRA
Country [33] 0 0
France
State/province [33] 0 0
Paris
Country [34] 0 0
Germany
State/province [34] 0 0
Bavaria
Country [35] 0 0
Germany
State/province [35] 0 0
DEU
Country [36] 0 0
Hungary
State/province [36] 0 0
HUN
Country [37] 0 0
Hungary
State/province [37] 0 0
Somogy
Country [38] 0 0
Hungary
State/province [38] 0 0
Zala
Country [39] 0 0
Hungary
State/province [39] 0 0
Gyula
Country [40] 0 0
Italy
State/province [40] 0 0
ITA
Country [41] 0 0
Italy
State/province [41] 0 0
Lombardy
Country [42] 0 0
Japan
State/province [42] 0 0
Aichi
Country [43] 0 0
Japan
State/province [43] 0 0
Chiba
Country [44] 0 0
Japan
State/province [44] 0 0
Ehime
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Hokkaido
Country [47] 0 0
Japan
State/province [47] 0 0
Kanagawa
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Sunto-gun
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo
Country [51] 0 0
Poland
State/province [51] 0 0
Masovia
Country [52] 0 0
Poland
State/province [52] 0 0
Podlaskie
Country [53] 0 0
Spain
State/province [53] 0 0
ESP
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Sevilla
Country [56] 0 0
Spain
State/province [56] 0 0
Valencia
Country [57] 0 0
United Kingdom
State/province [57] 0 0
GBR
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Middlesex

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hutchison Medipharma Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
William Schelman, MD, PhD
Address 0 0
HUTCHMED International Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04322539