Colorectal CarcinomaPhase 2NCT06603376
Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer
A Phase 2 study testing FOLFIRI + Vemurafenib + Cetuximab and FOLFIRI ± Bevacizumab in people with Colorectal Carcinoma, run by Shanghai Changzheng Hospital at 1 site in China.
Trial summary
Based on the upstream signaling features of BRAFV600E and the bypass feedback mechanisms, considering the pro-apoptotic effects of chemotherapy and the synergistic effects of targeted therapy, previous IMPROVEMENT trial creatively explored a balanced chemotherapy-targeted combination approach (FOLFIRI + Vemurafenib +… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Carcinoma
- What is being tested?
- FOLFIRI + Vemurafenib + Cetuximab and FOLFIRI ± Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2024to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with advanced colorectal adenocarcinoma confirmed by histology or cytology.
- Patients with BRAFV600E mutation confirmed by tissue or blood testing.
- Patients who have not received systemic therapy or who have experienced metastasis or recurrence 12 months after completing adjuvant therapy.
- Patients must have at least one measurable lesion according to RECIST 1.1 criteria.
- Patients who received local radiotherapy at least 3 weeks before the first drug treatment are allowed to enroll, but lesions evaluated by RECIST should not be within the radiation field.
- Patients aged ≥18 years and ≤80 years.
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- ECOG performance status of 0-2.
- Expected survival of ≥12 weeks.
- Patients must have the ability to understand and voluntarily sign a written informed consent.
- Women of childbearing potential must have a negative pregnancy test within 7 days prior to the start of treatment. During the study, both the patient and their partner must use contraception.
Who cannot join
- Patients who have undergone major surgery or suffered severe trauma within 4 weeks prior to the first dose of the study drug.
- Patients with hypersensitivity to any component of the study regimen.
- Patients who are planning to conceive or are already pregnant.
- Patients with brain metastases who cannot accurately describe their condition.
- Patients with the following conditions within 6 months prior to the start of the study treatment: myocardial infarction, severe/unstable angina, congestive heart failure greater than NYHA Class 2, uncontrolled arrhythmias, etc.
- Abnormal laboratory test results:
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- Absolute neutrophil count (ANC) \<1,500/mm³;
- Platelet count \<75,000/mm³;
- Total bilirubin \>1.5 times the upper limit of normal (ULN); ALT (alanine aminotransferase) and AST (aspartate aminotransferase) \>2.5 times ULN (for patients with liver metastasis \>5 times ULN); Creatinine \>1.5 times ULN;
- Patients who have had any cancer other than advanced colorectal cancer within five years prior to the start of the study treatment. Exceptions include cervical carcinoma in situ, cured basal cell carcinoma, and bladder epithelial tumors.
- Patients with a history of drug abuse, substance abuse, or alcohol dependence.
- Patients who are legally incapacitated or have limited civil capacity.
- Any other conditions deemed unsuitable for enrollment by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanghai Changzheng Hospital
Shanghai, 200004
Zang Wang, Professor, 8613916229609, 13916229609@139.com
About this study
Official title: A Randomized, Multicenter, Controlled Study of Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer
Based on the upstream signaling features of BRAFV600E and the bypass feedback mechanisms, considering the pro-apoptotic effects of chemotherapy and the synergistic effects of targeted therapy, previous IMPROVEMENT trial creatively explored a balanced chemotherapy-targeted combination approach (FOLFIRI + Vemurafenib + Cetuximab) in advanced colorectal cancer patients with BRAF V600E mutaiton using a signle-arm study design, demonstrating significant therapeutic efficacy in these patietns . To further validate the effectiveness and safety of this regimen and to solidify its clinical value, it is crucial to conduct a randomized, controlled trial. Investigators plan to use the current standard regimen as a control to compare this strategy (FOLFIRI + Vemurafenib + Cetuximab) on a large cohort of patients with BRAFV600E-mutant advanced colorectal cancer in the first-line setting, focusing on its efficacy and safety.
- Conditions
- Colorectal Carcinoma
- Being tested
- FOLFIRI + Vemurafenib + Cetuximab, FOLFIRI ± Bevacizumab
- Keywords
- colorectal cancer, BRAF V600E, chemotherpay, Vemurafenib, Cetuximab, irinotecan hydrochloride liposome injection
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFIRI + Vemurafenib + CetuximabDrug
Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Cetuximab: 500 mg/m², intravenous infusion over at least 2 hours, on day 1; Vemurafenib: 720 mg, orally twice daily. Repeat every 2 weeks.
FOLFIRI ± BevacizumabDrug
Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Bevacizumab: 5 mg/kg, intravenous infusion, on day 1. Repeat every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRI + Vemurafenib + Cetuximab | Experimental | Experimental Group: Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Cetuximab: 500 mg/m², intravenous infusion over at least 2 hours, on day 1; Vemurafenib: 720 mg, orally twice daily. Repeat every 2 weeks. Receives: Drug: FOLFIRI + Vemurafenib + Cetuximab |
| FOLFIRI ± Bevacizumab | Active comparator | Control Group: Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Bevacizumab: 5 mg/kg, intravenous infusion, on day 1. Repeat every 2 weeks. Receives: Drug: FOLFIRI ± Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission
Measured: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Secondary outcomes (3)
Progress Free Survival
Time from treatment beginning until disease progression or death from any cause
Measured: Evaluation of tumor burden based on RECIST criteria until first documented progress or death through study completion, an average of 8 weeks
Overall Survival
Time from treatment beginning until death from any cause
Measured: From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks
Deepness of response
Investigation of depth of response during first-line treatment
Measured: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Sep 2024
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by Shanghai Changzheng 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yuan-Sheng Zang, Shanghai Changzheng Hospital
- Investigators
- Yuan-Sheng Zang, Professor, Principal investigator, Shanghai Changzheng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06603376
- Sponsor's protocol ID
- IMPROVEMENT-2
- Status last verified
- Sep 2024
- First submitted
- 3 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Controlled Study of Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06603376
- Acronym / sponsor ID
- IMPROVEMENT-2
- Conditions
- Colorectal Carcinoma
- Keywords
- colorectal cancer, BRAF V600E, chemotherpay, Vemurafenib, Cetuximab, irinotecan hydrochloride liposome injection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Study start
- 1 Sep 2024 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 19 Sep 2024 (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.
Based on the upstream signaling features of BRAFV600E and the bypass feedback mechanisms, considering the pro-apoptotic effects of chemotherapy and the synergistic effects of targeted therapy, previous IMPROVEMENT trial creatively explored a balanced chemotherapy-targeted combination approach (FOLFIRI + Vemurafenib + Cetuximab) in advanced colorectal cancer patients with BRAF V600E mutaiton using a signle-arm study design, demonstrating significant therapeutic efficacy in these patietns . To further validate the effectiveness and safety of this regimen and to solidify its clinical value, it is crucial to conduct a randomized, controlled trial. Investigators plan to use the current standard regimen as a control to compare this strategy (FOLFIRI + Vemurafenib + Cetuximab) on a large cohort of patients with BRAFV600E-mutant advanced colorectal cancer in the first-line setting, focusing on its efficacy and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFIRI + Vemurafenib + Cetuximab | Experimental | Drug: FOLFIRI + Vemurafenib + CetuximabExperimental Group: Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Cetuximab: 500 mg/m², intravenous infusion over at least 2 hours, on day 1; Vemurafenib: 720 mg, orally twice daily. Repeat every 2 weeks. |
| FOLFIRI ± Bevacizumab | Active comparator | Drug: FOLFIRI ± BevacizumabControl Group: Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Bevacizumab: 5 mg/kg, intravenous infusion, on day 1. Repeat every 2 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with advanced colorectal adenocarcinoma confirmed by histology or cytology.
- Patients with BRAFV600E mutation confirmed by tissue or blood testing.
- Patients who have not received systemic therapy or who have experienced metastasis or recurrence 12 months after completing adjuvant therapy.
- Patients must have at least one measurable lesion according to RECIST 1.1 criteria.
- Patients who received local radiotherapy at least 3 weeks before the first drug treatment are allowed to enroll, but lesions evaluated by RECIST should not be within the radiation field.
Key exclusion criteria (13 listed)
- Patients who have undergone major surgery or suffered severe trauma within 4 weeks prior to the first dose of the study drug.
- Patients with hypersensitivity to any component of the study regimen.
- Patients who are planning to conceive or are already pregnant.
- Patients with brain metastases who cannot accurately describe their condition.
- Patients with the following conditions within 6 months prior to the start of the study treatment: myocardial infarction, severe/unstable angina, congestive heart failure greater than NYHA Class 2, uncontrolled arrhythmias, etc.
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 |
|---|---|---|
| FOLFIRI + Vemurafenib + CetuximabLiposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Cetuximab: 500 mg/m², intravenous infusion over at least 2 hours, on day 1; Vemurafenib: 720 mg, orally twice daily. Repeat every 2 weeks. | Drug | FOLFIRI + Vemurafenib + Cetuximab |
| FOLFIRI ± BevacizumabLiposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Bevacizumab: 5 mg/kg, intravenous infusion, on day 1. Repeat every 2 weeks. | Drug | FOLFIRI ± Bevacizumab |
Primary outcome
Objective response rate
Time frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission
3 secondary outcomes
Progress Free Survival
Time frame: Evaluation of tumor burden based on RECIST criteria until first documented progress or death through study completion, an average of 8 weeks
Overall Survival
Time frame: From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks
Deepness of response
Time frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 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.
Yuan-Sheng Zang, Professor principal investigator
Shanghai Changzheng Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FOLFIRI + Vemurafenib + Cetuximab and FOLFIRI ± Bevacizumab in people with Colorectal Carcinoma, run by Shanghai Changzheng 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 10 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 19 Sep 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhan Wang, Professor (86-13916229609, 13916229609@139.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (time frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks). 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 19 Sep 2024.