Fruquintinib Plus Capecitabine as Maintenance Treatment of RAS / BRAF Wild-type Metastatic Colorectal Cancer

August 17, 2022 updated by: Lin Yang, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

A Phase Ⅰb/Ⅱ Study of Fruquintinib Combined With Capecitabine in the First-line Maintenance Treatment of RAS/BRAF Wild-type Metastatic Colorectal Cancer

This phase I/II study was designed to evaluate the efficacy and safety of fruquintinib combination with capecitabine in maintenance treatment after first-line chemotherapy combined with cetuximab.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

At present, most studies use chemotherapy combined with cetuximab or cetuximab alone as the maintenance treatment scheme after the first-line regimen containing cetuximab. However, the skin reaction caused by cetuximab and frequent infusion treatment will bring inconvenience to patients. MACBETH study compared the maintenance of bevacizumab with cetuximab, although there was no significant difference in PFS between them, the Bev group seemed to convey a longer median OS. Fruquintinib is a highly selective anti angiogenesis TKI. This study aims to explore the efficacy and safety of fruquintinib combined with capecitabine in maintenance treatment after first-line chemotherapy combined with cetuximab. Both fruquintinib and capecitabine are orally given, so this regimen may provide a maintenance treatment option that is more manageable for patients in clinical practice.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • National Center/Cancer Hospital, China Academy of Medical Science and Peking Union Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with histologically confirmed metastatic colorectal adenocarcinoma;
  • 18-75 years old;
  • Eastern Cooperation Oncology Group (ECOG) performance score 0-1;
  • At least one evaluable lesion for disease assessment according to RECIST version 1.1;
  • Able to take oral medications;
  • Patient have achieved CR, PR or SD after up to 8 cycles of first-line standard FOLFOX / - FOLFIRI / XELOX / xeliri + cetuximab treatment, and remained unresectable;
  • If radiotherapy has been performed before enrollment, at least one lesion should be located outside the radiation field;
  • Adequate organ functions as assessed by the following laboratory requirements: Leukocytes≥3.0x10^9/L, absolute neutrophil count≥1.5x10^9/L, platelet count≥100x10^9/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit of normal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤2.5x ULN; serum creatinine≤1.5x ULN.
  • An expected survival of at least 12 weeks;
  • Fertile male or female patients volunteered to use effective contraceptive methods during the study period and within 6 months after the end of treatment;
  • Willing to provide written informed consent to study procedures.

Exclusion Criteria:

  • Patients who have received fruquintinib;
  • Patients who have received TACE within 6 weeks before enrollment;
  • Participated in other unapproved or unlisted drug clinical trials in China within 4 weeks before enrollment, and received corresponding experimental drug treatment;
  • Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
  • International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN；
  • The researchers judged clinically significant electrolyte abnormalities;
  • At present, the patient has hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
  • Patients currently have poorly controlled diabetes (fasting glucose level is greater than CTCAE grade 2 after regular treatment);
  • Have received any surgery or invasive treatment or operation within 4 weeks before enrollment (except venous catheterization, puncture and drainage, etc.);
  • Active or uncontrolled severe infection ≥ grade 2 according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
  • Uncontrolled central nervous system metastasis or previous brain metastasis;
  • Other malignant tumors in the past 5 years, except for skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
  • Any kind of concurrent cardiac disease with clinical meanings, such as cardiovascular accident, myocardial infarction, thromboembolism or hemorrhage within 6 months before enrollment, congestive heart failure ≤New York Heart Association (NYHA) class 2; ventricular arrhythmias requiring drug treatment; LVEF < 50%;
  • With positive urine protein and 24-hour urinary protein content>1g;
  • Have a tendency of bleeding or clotting;
  • Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis;
  • The target lesions have received brachytherapy (radioactive particle implantation) within 60 days before admission;
  • Unrelieved toxic reactions higher than CTCAE V5.0 grade 1 caused by any previous anti-cancer treatment, excluding hair loss, lymphopenia and neurotoxicity ≤ grade 2 caused by oxaliplatin;
  • With any illness or medical conditions that may jeopardize the patient's compliance or interfere the analyses or judgements of study results;
  • Pregnancy or lactation at the time of study entry;
  • With fertility but refuse to contraception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Experimental
fruquintinib plus capecitabine
Drug: fruquintinib plus capecitabine

Ⅰb: capecitabine: 1000 mg/m²，PO BID, d1-14，Q3W; fruquintinib 3mg/4mg/5mg, d1-14, PO QD, Q3W.

ⅠⅠ: fruquintinib RP2D, d1-14, PO QD, Q3W, capecitabine: 1000 mg/m²，PO BID, d1-14，Q3W

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
recommended phase 2 dose (RP2D)
Time Frame: up to 1 year
RP2D is determined according to DLT and MTD in the phase 1 study
up to 1 year
progression-free survival (PFS)
Time Frame: up to 3 years
PFS is defined as the time from the start of maintenance treatment to the earliest evidence of disease progression (per RECIST v1.1), or death from any cause
up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
disease control rate (DCR)
Time Frame: up to 3 years
DCR is defined as the proportion of patients achieving complete response, partial response or having stable disease
up to 3 years
objective response rate (ORR)
Time Frame: up to 3 years
ORR is defined as the proportion of patients achieving complete response or partial response
up to 3 years
overall survival (OS)
Time Frame: up to 3 years
OS is defined as the time from randomized to death from any cause or to last contact
up to 3 years
Adverse events (AEs)
Time Frame: up to 3 years
Adverse events assessments are computed and categorized according to the Common Toxicity Criteria of the National Cancer Institute, version 5.0
up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 12, 2022

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2023

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 17, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2021

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 23, 2021

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HMPL-013-FLAG-C102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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