Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Patients With Metastatic Colorectal Cancer (FRESCO-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04322539
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : September 14, 2020
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Brief Summary:
This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). Approximately 520 subjects will be randomized to one of the following treatment arms in a 2:1 ratio, fruquintinib plus BSC or placebo plus BSC.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Metastatic Colon Cancer Drug: Fruquintinib Drug: Placebo Phase 3

Detailed Description:

This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib in combination with BSC versus placebo in combination with BSC in advanced colorectal cancer patients who have progressed on, or were intolerant to, chemotherapy, biologics, and TAS-102 or regorafenib. Patients with MSI-H/MMR deficient tumors must have also received an immune checkpoint inhibitor if approved and available and if deemed appropriate.

Metastatic colorectal cancer cannot be cured by surgery. Therefore, treatment principals are primarily aimed at controlling disease progression and prolonging survival. Standard first- and second-line therapy includes cytotoxic drugs such as 5-fluorouracil, oxaliplatin, and irinotecan; anti-VEGF therapy; and, if RAS wild type, anti-EGFR therapy. After the first two lines of chemotherapy, standard third-line treatment is either TAS-102 or regorafenib. There are currently no effective treatments for patients who have progressed on standard, approved therapies, and treatment options include reuse of prior therapies, clinical trials or BSC. Consequently, there is an unmet medical need for additional safe and effective treatment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 522 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : July 10, 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: fruquintinib plus best supportive care
In this arm, subjects will receive active study drug plus best supportive care
Drug: Fruquintinib
Oral VEGFR inhibitor
Other Name: HMPL-013

Placebo Comparator: placebo plus best supportive care
In this arm, subjects will receive placebo plus best supportive care
Drug: Placebo
Placebo capsule




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: up to 10 years ]
    To evaluate the overall survival of fruquintinib plus BSC compared to placebo plus BSC in subjects with refractory mCRC.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;
  • Subjects must have progressed on or been intolerant to treatment with either trifluridine/tipiracil (TAS-102) or regorafenib. Subjects 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. Subjects who have been treated with both TAS-102 and regorafenib are permitted. Subjects 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;
  • Subjects 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 subject's country unless the patient is ineligible for treatment with a checkpoint inhibitor;
  • Subjects who received oxaliplatin in the adjuvant setting must have progressed within 6 months of completion of adjuvant therapy;
  • 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 subjects of childbearing potential and male subjects 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 together with a barrier method (eg, diaphragm, always containing a spermicide), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or sexual abstinence. Oral contraception should always be combined with an additional contraceptive method (ie, barrier method) because of a potential interaction with the study drug. The same criteria are applicable to male subjects involved in this clinical trial if they have a partner of childbirth potential, and male subjects must always use a condom.

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). Patients with Gilbert syndrome, bilirubin <2 X ULN, and normal AST/ALT are eligible;
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × ULN in patients without hepatic metastases; ALT or AST >5 × ULN in patients 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. Subjects with greater than 1+ proteinuria on urinalysis must undergo a 24-hour urine collection;
  • Uncontrolled hypertension, defined as: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg despite optimal medical management;
  • 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 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 patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients 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; patients 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 any of its inactive ingredients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04322539


Contacts
Layout table for location contacts
Contact: Alberto Fernandez +1-973-567-3891 albertof@hmplglobal.com

Locations
Show Show 34 study locations
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
Layout table for investigator information
Study Director: William Schelman, MD, PhD Hutchison MediPharma International
Layout table for additonal information
Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT04322539    
Other Study ID Numbers: 2019-013-GLOB1
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: September 14, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hutchison Medipharma Limited:
colon
colorectal
mcrc
crc
metastatic colon
metastatic colorectal
VEGF
VEGFR
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases