Colorectal CancerPhase 2NCT05511051
A Prospective Multi-centered Randomized Controlled Trial on Fruquintinib in Combination With HAIC in the Treatment of Liver Metastatic Colorectal Cancer After Failure of Second-line Systematic Therapy
A Phase 2 study testing Fruquintinib and HAIC in people with Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 3 sites in China.
Trial summary
The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Fruquintinib and HAIC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 3 sitesChina
- Study dates
- 1 Feb 2022to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fully understand the study and voluntarily sign the informed consent form;
- Age ≥ 18 years;
- Patients with unresectable colorectal liver metastases who have failed standard second-line systemic therapy, who have not previously received HAIC therapy, and have not received third-line standard targeted agents (regorafenib or fruquintinib or trifluridine tipiracil (TAS-102);
- Definition of liver metastases: at least 1 measurable liver metastasis lesion (based on RECIST 1.1); if the liver metastases are single, the tumor is > 5 cm; if multiple tumors, it needs to be greater than or equal to 4, of which at least 1 exceeds 3 cm;
- PFS > 4 months from last dose of oxaliplatin with FOLFOX regimen
- Child-Pugh classification of liver function: A;
Show all 21Show fewer
- ECOG performance status 0-1, and no deterioration within 7 days;
- BMI ≥ 18;
- Expected survival ≥ 3 months;
- Vital organs function in accordance with the following requirements (any blood components and cell growth factors are not allowed within 14 days before enrollment):
- Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L;
- Platelets ≥ 100 × 109/L;
- Hemoglobin ≥ 90 g/L;
- Total bilirubin TBIL ≤ 1.5 times ULN;
- ALT and AST ≤ 5 times ULN;
- Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN (and creatinine clearance (CCr) ≥ 50 mL/min);
- Left ventricular ejection fraction (LVEF) ≥ 50%;
- Fridericia-corrected QT interval (QTcF) < 470 milliseconds.
- INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN.
- women of childbearing age need to take effective contraceptive measures;
- good compliance and cooperation with follow-up.
Who cannot join
- Unable to comply with the study protocol or study procedures;
- Pregnant or breastfeeding women;
- Any factor affecting oral administration;
- Evidence of central nervous system metastases;
- Concurrent with any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure;
- Alcohol or drug abuse within 4 weeks after the last clinical trial;
Show all 26Show fewer
- Previous VEGFR inhibition therapy;
- Uncontrolled severe concurrent infection resulting in disability;
- Proteinuria ≥ 2 + (1.0 g/24 h);
- Evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of seriousness;
- Arterial/venous thromboembolic events, such as cerebrovascular accidents (including transient ischemic attack), within 12 months before the first treatment;
- Acute myocardial infarction, acute coronary syndrome or CABG within 6 months before the first treatment;
- Fractures or wounds that have not been cured for a long time;
- coagulopathy, bleeding tendency or receiving anticoagulant therapy;
- Inactivated vaccines within 4 weeks prior to enrollment or possible during the study;
- Patients with other malignant tumors within 5 years before enrollment, except for basal cell or squamous cell carcinoma of the skin after radical resection, or cervical carcinoma in situ;
- Active autoimmune diseases or history of autoimmune diseases within 4 weeks before enrollment;
- Previous allogeneic bone marrow transplantation or organ transplantation;
- Subjects who are allergic to the study drug or any of its adjuvant preparations;
- Electrolyte abnormalities judged clinically significant by the investigator;
- Known human immunodeficiency virus (HIV) infection. Known history of clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must have excluded active HBV infection, ie, positive HBV DNA (> 1 × 104 copies/mL or > 2000 IU/mL); known hepatitis C virus (HCV) infection and positive HCV RNA (> 1 × 103 copies/mL);
- Unresolved toxicities above CTCAE v5.0 grade 1 due to any prior anticancer therapy, excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2;
- Received blood transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before enrollment;
- with brain metastases, or with severe malignant pleural effusion and ascites;
- Any other diseases, clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the investigator 's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for the use of the study drug (such as having seizures and requiring treatment), or will affect the interpretation of the study results, or put the patient at high risk;
- Patients who are considered unsuitable for inclusion in this study by the investigator.
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing
Yue Han, +86-13511021629, doctorhan@163.com
- Not yet recruiting
Dalian Medial University Affiliated Second Hospital
Dalian
Jinghua Sun
- Not yet recruiting
People's Hospital of Inner Mongolia
Hohhot
Liying Xue
About this study
Official title: A Prospective Multi-centered Randomized Controlled Trial on Fruquintinib in Combination With Hepatic Arterial Infusion Chemotherapy (HAIC) in the Treatment of Liver Metastatic Colorectal Cancer After Failure of Second-line Systematic Therapy
The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver metastases.
Read the detailed description
Among Chinese colorectal cancer patients, 43.8% had metastasis at the time of diagnosis, of which liver metastasis accounted for 51.5%. In addition, it was reported that 10%-25% of patients developed liver metastasis after radical resection of colorectal cancer, and more than two-thirds of colorectal patients eventually developed liver metastasis. Colorectal liver metastasis was reported to be the most important cause of death in colorectal cancer patients.The median survival time of untreated liver metastases was only 6.9 months, and the 5-year survival rate of unresectable patients was less than 5%, and for unresectable colorectal liver metastasis, the median survival time could reach 30.9 months after comprehensive treatment.
Fruquintinib, a VEGFR 1/2/3 inhibitor, is one of the standard 3rd-line therapy for colorectal cancer, which has already been approved and marketed in China. In phase III FRESCO study, liver metastases subgroup showed that the median OS of fruquintinib group was 8.61 months, which was 2.63 months longer than that of control group, reducing death risk by 41%, with statistically significant P value.
Patients with large tumor burden mainly caused by liver metastasis and with insignificant or refractory response to drug therapy, or patients who cannot tolerate systemic therapy, can be combined with transcatheter arterial chemoembolization (HAI) or transcatheter arterial chemoembolization (TACE) at appropriate time, which helps to prolong the progression-free time and overall survival.
The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver metastases.
- Conditions
- Colorectal Cancer
- Being tested
- Fruquintinib, HAIC
- Keywords
- Third-line
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FruquintinibDrug
Fruquintinib
HAICDrug
HAIC
| Study group | Role | What they receive |
|---|---|---|
| Fruquintinib + HAIC | Experimental | Fruquintinib: 5 mg orally once daily for 21 days on followed by 7 days off (q4w); HAIC: oxaliplatin 100 mg/m2, leucovorin calcium 200 mg/m2, fluorouracil 2000 mg/m2 24-hour drip, q4w, 2 cycles; HAIC treatment was administered during fruquintinib rest; HAIC was discontinued 1 day before surgery, on the day of completion of surgery, and 5 days after surgery; Receives: Drug: Fruquintinib; Drug: HAIC |
| Fruquintinib | Active comparator | Fruquintinib: 5 mg orally once daily for 21 days on followed by 7 days off (q4w); Receives: Drug: Fruquintinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
every two months after end of treatment (EOT) observation period at 30 days after the last medication every two months after end of treatment (EOT) observation period at 30 days after the last medication every two months after end of treatment (EOT) observation period at 30 days after the last medication
Measured: from randomization until death due to any cause, assessed up to 2 year
Secondary outcomes (3)
Progress-free Survival
Tumor assessment will be performed using radiography method every 8 weeks, until the occurrence of progressive disease (PD), using RECIST v 1.1
Measured: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Objective Response Rate
Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1
Measured: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Safety and tolerance evaluated by incidence, severity and outcomes of AEs
Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.
Measured: from first dose to within 30 days after the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2022
- Study start1 Feb 2022
- Primary completion1 Aug 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Hutchison Medipharma Limited
- Responsible party
- Principal investigator, Yue Han, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05511051
- Sponsor's protocol ID
- HMPL-013-N1-CRC102
- Status last verified
- Aug 2022
- First submitted
- 19 Aug 2022
- Last updated
- 22 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multi-centered Randomized Controlled Trial on Fruquintinib in Combination With Hepatic Arterial Infusion Chemotherapy (HAIC) in the Treatment of Liver Metastatic Colorectal Cancer After Failure of Second-line Systematic Therapy
- ClinicalTrials.gov ID
- NCT05511051
- Acronym / sponsor ID
- HMPL-013-N1-CRC102
- Conditions
- Colorectal Cancer
- Keywords
- Third-line
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Collaborators
- Hutchison Medipharma Limited
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Aug 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 22 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver metastases.
Detailed description
Among Chinese colorectal cancer patients, 43.8% had metastasis at the time of diagnosis, of which liver metastasis accounted for 51.5%. In addition, it was reported that 10%-25% of patients developed liver metastasis after radical resection of colorectal cancer, and more than two-thirds of colorectal patients eventually developed liver metastasis. Colorectal liver metastasis was reported to be the most important cause of death in colorectal cancer patients.The median survival time of untreated liver metastases was only 6.9 months, and the 5-year survival rate of unresectable patients was less than 5%, and for unresectable colorectal liver metastasis, the median survival time could reach 30.9 months after comprehensive treatment.
Fruquintinib, a VEGFR 1/2/3 inhibitor, is one of the standard 3rd-line therapy for colorectal cancer, which has already been approved and marketed in China. In phase III FRESCO study, liver metastases subgroup showed that the median OS of fruquintinib group was 8.61 months, which was 2.63 months longer than that of control group, reducing death risk by 41%, with statistically significant P value.
Patients with large tumor burden mainly caused by liver metastasis and with insignificant or refractory response to drug therapy, or patients who cannot tolerate systemic therapy, can be combined with transcatheter arterial chemoembolization (HAI) or transcatheter arterial chemoembolization (TACE) at appropriate time, which helps to prolong the progression-free time and overall survival.
The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fruquintinib + HAIC | Experimental | Drug: Fruquintinib, Drug: HAICFruquintinib: 5 mg orally once daily for 21 days on followed by 7 days off (q4w); HAIC: oxaliplatin 100 mg/m2, leucovorin calcium 200 mg/m2, fluorouracil 2000 mg/m2 24-hour drip, q4w, 2 cycles; HAIC treatment was administered during fruquintinib rest; HAIC was discontinued 1 day before surgery, on the day of completion of surgery, and 5 days after surgery; |
| Fruquintinib | Active comparator | Drug: FruquintinibFruquintinib: 5 mg orally once daily for 21 days on followed by 7 days off (q4w); |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Fully understand the study and voluntarily sign the informed consent form;
- Age ≥ 18 years;
- Patients with unresectable colorectal liver metastases who have failed standard second-line systemic therapy, who have not previously received HAIC therapy, and have not received third-line standard targeted agents (regorafenib or fruquintinib or trifluridine tipiracil (TAS-102);
- Definition of liver metastases: at least 1 measurable liver metastasis lesion (based on RECIST 1.1); if the liver metastases are single, the tumor is > 5 cm; if multiple tumors, it needs to be greater than or equal to 4, of which at least 1 exceeds 3 cm;
- PFS > 4 months from last dose of oxaliplatin with FOLFOX regimen
Key exclusion criteria (26 listed)
- Unable to comply with the study protocol or study procedures;
- Pregnant or breastfeeding women;
- Any factor affecting oral administration;
- Evidence of central nervous system metastases;
- Concurrent with any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FruquintinibFruquintinib | Drug | Fruquintinib, Fruquintinib + HAIC |
| HAICHAIC | Drug | Fruquintinib + HAIC |
Primary outcome
Overall Survival
Time frame: from randomization until death due to any cause, assessed up to 2 year
every two months after end of treatment (EOT) observation period at 30 days after the last medication every two months after end of treatment (EOT) observation period at 30 days after the last medication every two months after end of treatment (EOT) observation period at 30 days after the last medication
3 secondary outcomes
Progress-free Survival
Time frame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Objective Response Rate
Time frame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Safety and tolerance evaluated by incidence, severity and outcomes of AEs
Time frame: from first dose to within 30 days after the last dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Individual participant dataSharing planned: No
Related trials for Colorectal Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
Active, not recruitingObservational study
The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer
Prostate Cancer, BRCA Mutation
RecruitingObservational study
ABCSG R07 Rectal Cancer Registry
Rectal Cancer, Adenocarcinoma of Rectum
Recruiting
Mainstreaming Genetics: Evaluation of a Digital Application to Scale and Spread Oncologist-initiated Genetic Testing
Cancer, Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, China
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fruquintinib and HAIC in people with Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: from randomization until death due to any cause, assessed up to 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.