Metastatic Colorectal CancerPhase 1/2NCT05522738
Safety and Efficacy of Fruquintinib+FOLFIRI in RAS-mutated Metastatic Colorectal Cancer
A Phase 1/2 study testing Combination: Fruquintinib + FOLFIRI in people with Metastatic Colorectal Cancer, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Molecular subtypes make difference on clinicopathologic features and response to chemotherapy and targeted agents as well as prognosis. RAS mutation status, which accounting for approximately 35% to 40% of colorectal cancer patients, is an important factor considered in the standard of care for colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Combination: Fruquintinib + FOLFIRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteChina
- Study dates
- 10 Aug 2022to Dec 2025
- Phase
- Phase 1/2
- 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;
- Pathologically confirmed unresectable metastatic colorectal cancer;
- Known RAS gene mutations;
- failed standard first-line FOLFOX/XELOX combined with bevacizumab;
- ECOG performance status 0-1;
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- BMI ≥ 18;
- Expected survival ≥ 3 months;
- Vital organ function meets 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 x 109/L;
- Hemoglobin ≥ 90 g/L;
- Total bilirubin TBIL ≤ 1.5 × ULN;
- ALT and AST ≤ 5 x ULN;
- Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 x ULN (and creatinine clearance (CCr) ≥ 50 mL/min);
- Left ventricular ejection fraction (LVEF) > = 50%;
- Fridericia corrected QT interval (QTcF) < 470 milliseconds.
- INR ≤ 1.5 x ULN, APTT ≤ 1.5 x ULN.
- Women of childbearing age should take effective contraceptive measures;
- Good compliance and cooperation with follow-up.
Who cannot join
- Unable to comply with the study protocol or study procedures;
- Known BRAF gene mutations;
- evidence of central nervous system metastasis, or associated with severe malignant pleural effusion and ascites;
- Previous treatment with irinotecan;
- previous treatment with VEGFR inhibitor
- Concurrent use of any other investigational drug, or enrollment in a clinical trial of other investigational drug therapy within 4 weeks before enrollment;
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- Inactivated vaccines within 4 weeks before enrollment or possibly during the study;
- patients in the study group underwent major surgery or severe traumatic injury, fracture or ulcer within 4 weeks;
- Receiving blood transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before enrollment;
- Alcohol or drug abuse within 4 weeks prior to enrollment;
- Any factor affecting oral administration;
- Concurrent any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure;
- Uncontrollable serious concurrent infections resulting in disability;
- Proteinuria ≥ 2 + (1.0 g/24 h)
- Evidence or history of bleeding tendency within 2 months before 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 prior to the first treatment;
- Fractures or wounds that have not been healed for a long time;
- Coagulopathy, bleeding tendency, or ongoing anticoagulant therapy;
- Patients with other malignant tumors within 5 years before enrollment, except for skin basal cell carcinoma or squamous cell carcinoma after radical resection, or cervical carcinoma in situ;
- Active autoimmune disease or history of autoimmune disease 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 excipients;
- clinically significant electrolyte abnormalities judged 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;
- 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;
- Pregnant or lactating females;
- Patients who the investigator considers inappropriate for inclusion in this study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing
Guanghai Dai, +8666947252, daigh301@vip.sina.com
Guanghai Dai
About this study
Official title: Prospective, Single-arm, Single-center Phase Ib/II Trial on the Safety and Efficacy of Fruquintinib in Combination With FOLFIRI in RAS-mutated Metastatic Colorectal Cancer
Molecular subtypes make difference on clinicopathologic features and response to chemotherapy and targeted agents as well as prognosis. RAS mutation status, which accounting for approximately 35% to 40% of colorectal cancer patients, is an important factor considered in the standard of care for colorectal cancer. For RAS-mutated patients, no targeted driver gene drugs have been approved, and their treatment is based on the anti-VEGF/VEGFR pathway, and corresponding targeted drugs such as bevacizumab, aflibercept, and ramucirumab have also been successfully marketed for the treatment of CRC.
For RAS mutant metastatic colorectal cancer, the commonly used first-line treatment regimen is bevacizumab combined with chemotherapy, which is shown in previous studiesthat the PFS of 1st-line is about 10 months; the standard regimen of second-line treatment is FOLFIRI ± bevacizumab, which is shown in previous study that the 2nd-line PFS is about 5 months with ORR 4%. There are a lot of unmet medical needs to improve the clinical efficacy in secondline-treatment of RAS-mutant patients.
Read the detailed description
This is a prospective, single-armed, single-center phase Ib/II study to investigate the safety and efficacy of Fruquintinib combined with FOLFIRI in RAS-mutant patients who failed first-line standard therapy.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Combination: Fruquintinib + FOLFIRI
- Keywords
- RAS-mutant, second-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.
Combination: Fruquintinib + FOLFIRIDrug
Also called Elunate, HMPL-013
Phase 1b Fruquintinib was administered in a 3 + 3 dose escalation regimen at the following doses: L1:3 mg/d, L2:4 mg/d, L3:5 mg/d.
Fruquintinib: QD po q2w
FOLFIRI regimen:
Irinotecan:180 mg/m2, i.v. , d1, q2w LV:200 mg/m2, i.v., d1, q2w 5-FU:2400 mg/m2, i.v.for over 46 hours, q2w
Phase II Fruquintinib: RP2D, QD po q2w
FOLFIRI regimen:
Irinotecan: 180 mg/m2, i.v. , d1, q2w LV: 200 mg/m2, i.v., d1, q2w 5-FU:2400 mg/m2, i.v.for over 46 hours, q2w
| Study group | Role | What they receive |
|---|---|---|
| study group | Experimental | Fruquintinib combined with FOLFIRI Receives: Drug: Combination: Fruquintinib + FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 treatment initiation to progressive disease or EOT due to any cause, assessed up to 1 year
RP2D
RECIST v1.1
Measured: from first dose up to progressive disease or EOT due to any cause, assessed up to 1 year
Secondary outcomes (5)
Overall Survival
every two months follow up after EOT observation period at 30 days after the last medication
Measured: from treatment initiation until death due to any cause, assessed up to 3 year
Progress-Free Survival
every two months follow up after EOT observation period at 30 days after the last medication
Measured: from treatment initiation until death due to any cause, assessed up to 2 year
Duration of Response
every two months follow up after EOT observation period at 30 days after the last medication
Measured: from treatment initiation until death due to any cause, assessed up to 2 year
Safety and tolerance evaluated by incidence of AE
Incidence and severity of AE
Measured: from first dose to 30 days post the last dose
Safety and tolerance evaluated by incidence of SAE
Incidence and severity of SAE
Measured: from first dose to 30 days post 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 posted31 Aug 2022
- Study start10 Aug 2022
- Primary completionDec 2024 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Hutchison Medipharma Limited
- Responsible party
- Principal investigator, Dai, Guanghai, Chinese PLA General Hospital
- Investigators
- Guanghai Dai, Doctor, Principal investigator, Chinese PLA General HospitalQuanli Han, Doctor, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05522738
- Sponsor's protocol ID
- HMPL-013-N1-CRC104
- Status last verified
- Jan 2024
- First submitted
- 23 Aug 2022
- Last updated
- 8 Jan 2024
- Results posted
- No
- Data monitoring committee
- 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 8 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single-arm, Single-center Phase Ib/II Trial on the Safety and Efficacy of Fruquintinib in Combination With FOLFIRI in RAS-mutated Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05522738
- Acronym / sponsor ID
- HMPL-013-N1-CRC104
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- RAS-mutant, second-line
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Collaborators
- Hutchison Medipharma Limited
- Study start
- 10 Aug 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 31 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.
Molecular subtypes make difference on clinicopathologic features and response to chemotherapy and targeted agents as well as prognosis. RAS mutation status, which accounting for approximately 35% to 40% of colorectal cancer patients, is an important factor considered in the standard of care for colorectal cancer. For RAS-mutated patients, no targeted driver gene drugs have been approved, and their treatment is based on the anti-VEGF/VEGFR pathway, and corresponding targeted drugs such as bevacizumab, aflibercept, and ramucirumab have also been successfully marketed for the treatment of CRC.
For RAS mutant metastatic colorectal cancer, the commonly used first-line treatment regimen is bevacizumab combined with chemotherapy, which is shown in previous studiesthat the PFS of 1st-line is about 10 months; the standard regimen of second-line treatment is FOLFIRI ± bevacizumab, which is shown in previous study that the 2nd-line PFS is about 5 months with ORR 4%. There are a lot of unmet medical needs to improve the clinical efficacy in secondline-treatment of RAS-mutant patients.
Detailed description
This is a prospective, single-armed, single-center phase Ib/II study to investigate the safety and efficacy of Fruquintinib combined with FOLFIRI in RAS-mutant patients who failed first-line standard therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study group | Experimental | Drug: Combination: Fruquintinib + FOLFIRIFruquintinib combined with FOLFIRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Fully understand the study and voluntarily sign the informed consent form;
- Age ≥ 18 years;
- Pathologically confirmed unresectable metastatic colorectal cancer;
- Known RAS gene mutations;
- failed standard first-line FOLFOX/XELOX combined with bevacizumab;
Key exclusion criteria (29 listed)
- Unable to comply with the study protocol or study procedures;
- Known BRAF gene mutations;
- evidence of central nervous system metastasis, or associated with severe malignant pleural effusion and ascites;
- Previous treatment with irinotecan;
- previous treatment with VEGFR inhibitor
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 |
|---|---|---|
| Combination: Fruquintinib + FOLFIRIAlso: Elunate, HMPL-013Phase 1b Fruquintinib was administered in a 3 + 3 dose escalation regimen at the following doses: L1:3 mg/d, L2:4 mg/d, L3:5 mg/d. Fruquintinib: QD po q2w FOLFIRI regimen: Irinotecan:180 mg/m2, i.v. , d1, q2w LV:200 mg/m2, i.v., d1, q2w 5-FU:2400 mg/m2, i.v.for over 46 hours, q2w Phase II Fruquintinib: RP2D, QD po q2w FOLFIRI regimen: Irinotecan: 180 mg/m2, i.v. , d1, q2w LV: 200 mg/m2, i.v., d1, q2w 5-FU:2400 mg/m2, i.v.for over 46 hours, q2w | Drug | study group |
Primary outcome
Objective Response Rate
Time frame: From treatment initiation to progressive disease or EOT due to any cause, assessed up to 1 year
Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1
RP2D
Time frame: from first dose up to progressive disease or EOT due to any cause, assessed up to 1 year
RECIST v1.1
5 secondary outcomes
Overall Survival
Time frame: from treatment initiation until death due to any cause, assessed up to 3 year
Progress-Free Survival
Time frame: from treatment initiation until death due to any cause, assessed up to 2 year
Duration of Response
Time frame: from treatment initiation until death due to any cause, assessed up to 2 year
Safety and tolerance evaluated by incidence of AE
Time frame: from first dose to 30 days post the last dose
Safety and tolerance evaluated by incidence of SAE
Time frame: from first dose to 30 days post 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 8 Jan 2024.
- Individual participant dataSharing planned: No
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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.
Guanghai Dai, Doctor principal investigator
Chinese PLA General Hospital
Quanli Han, Doctor principal investigator
Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Combination: Fruquintinib + FOLFIRI in people with Metastatic Colorectal Cancer, run by Chinese PLA General Hospital at 1 site 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 20 inclusion and 29 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 8 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Objective Response Rate (time frame: From treatment initiation to progressive disease or EOT due to any cause, assessed up to 1 year). The study lists 2 primary outcomes in all. 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 8 Jan 2024.