Metastatic Colorectal CancerPhase 1NCT06225622
Dose Escalation and Expansion Clinical Trial of Irinotecan Liposome Combined With Oxaliplatin and 5-FU/LV Plus Bevacizumab as First-line Treatment of Metastatic Colorectal Cancer
A Phase 1 study testing Irinotecan Liposome, Oxaliplatin and 5-FU in people with Metastatic Colorectal Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
Dose escalation clinical trial: To explore the dose limiting toxicity (DLT) of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab in first-line treatment of patients with advanced metastatic colorectal cancer, and to estimate the maximum tolerated dose (MTD) of combined administration. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Irinotecan Liposome, Oxaliplatin and 5-FU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteChina
- Study dates
- 11 Mar 2024to 1 May 2026
- Phase
- Phase 1
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-75 years old.
- Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma.
- The unresectable stage of metastatic disease has not received any systemic antitumor therapy.
- For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 12 months removed from the date of last administration of neoadjuvant or adjuvant therapy.
- The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria.
- ECOG 0
- Normal bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×10^9/L, platelets (PLT) ≥100×10^9/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×10^9/L, albumin (ALB) ≥35 g/L, and no bleeding tendency; ② AST, ALT and alkaline phosphatase (ALP) were all ≤2.5× upper limit of normal range (ULN), and ≤5×ULN when liver metastases occurred; The total bilirubin level doesn't exceed the upper limit of the agency's normal range; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated according to Cockroft-Gault)
- Understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form.
Who cannot join
- Patients with known MSI-H or dMMR who were evaluated by investigators as suitable for treatment with immune checkpoint inhibitors.
- Patients allergic to the investigational drug and its excipients.
- Underweight (body mass index [BMI]<18.5 kg/m^2).
- Known or suspected central nervous system metastasis.
- Received irinotecan before enrollment.
- Had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment.
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- Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 class I or below.
- The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment.
- Serious gastrointestinal disorders.
- Interstitial lung disease.
- Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding).
- Patients with fluid accumulation that couldn't reach a stable state and small amount of pleural effusion or ascites on imaging without clinical symptoms could be enrolled.
- Intestinal obstruction, signs and symptoms of intestinal obstruction, or the stent has been previously implanted and the stent has not been removed before the screening period.
- Gastrointestinal perforation, intraperitoneal abscess, and fistula.
- Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc.
- Have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer.
- Patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding.
- The researchers didn't consider it appropriate to participate in this study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200032
Tianshu Liu, Doctor
About this study
Dose escalation clinical trial: To explore the dose limiting toxicity (DLT) of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab in first-line treatment of patients with advanced metastatic colorectal cancer, and to estimate the maximum tolerated dose (MTD) of combined administration.
Expansion clinical trial: To evaluate the safety and efficacy of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab in first-line treatment of patients with advanced metastatic colorectal cancer. Exploratory analysis of ctDNA changes and genetic mutations in patients at baseline.
Read the detailed description
This is a dose escalation and expansion study to evaluate the safety and efficacy of irinotecan liposome injection in patients with first-line treatment for metastatic colorectal cancer. In the dose escalation phase, patients will be treated with a combination regimen of irinotecan liposome injection at doses of 60mg/m2, 70mg/m2, and 80mg/m2, and 9 to 18 eligible patients are expected to be enrolled. In the expansion phase, approximately 60 patients will receive combination therapy with irinotecan liposome RP2D dose and exploratory analysis of genetic mutations at baseline and ctDNA changes during treatment.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Irinotecan Liposome, Oxaliplatin, 5-FU, LV, Bevacizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan LiposomeDrug
In dose escalation study, irinotecan liposome injection will be administered by an intravenous infusion at three doses of 60 mg/m2, 70 mg/m2 and 80 mg/m2, d1, 14 days per cycle. In expansion study, irinotecan liposome injection will be administered by an intravenous infusion at the dose of RP2D, d1, 14 days per cycle.
Until the disease progresses or surgery is possible.
OxaliplatinDrug
85 mg/m2, intravenously infusion, d1, 14 days per cycle, up to 12 cycles.
5-FUDrug
2400mg/m2, intravenous infusion, d1-2, 14 days per cycle. Until the disease progresses or surgery is possible.
LVDrug
400mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.
BevacizumabDrug
5mg/kg, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.It is used to patients in dose escalation phase and with gene mutation in extension phase.
CetuximabDrug
500mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.For wild-type patients in extended phase studies.
| Study group | Role | What they receive |
|---|---|---|
| irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab | Experimental | In dose escalation study, patients will be treated with irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab. In expansion study, patients will be treated with irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab, depending on their baseline mutation status. Oxaliplatin is accepted up to 12 cycles. Receives: Drug: Irinotecan Liposome; Drug: Oxaliplatin; Drug: 5-FU; Drug: LV; Drug: Bevacizumab; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated dose
To investigate the safety.
Measured: Up to 14 days
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
To evaluate the incidence and severity of hematological adverse events in patients.
Measured: Start by signing the informed consent form until 4 weeks after the last dose.
Secondary outcomes (4)
Objective response rate
To investigate the preliminary antitumor efficacy of study.
Measured: From initial medication to the date of first documented progression or end of medication, assessed up to 20 months.
Disease control rate
To investigate the preliminary antitumor efficacy of study.
Measured: From initial medication to the date of first documented progression or end of medication , assessed up to 20 months.
Progression free survival
To investigate the preliminary antitumor efficacy of study.
Measured: From initial medication to the date of first documented progression or date of death from any cause, whichever came first , assessed up to 22 months.
R0 resection
To assess surgical conversion rates in patients who could be surgically resected.
Measured: From the first dose to the surgery, assessed up to 22 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start11 Mar 2024
- Primary completion1 Jan 2026 (estimated)
- Study completion1 May 2026 (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 Shanghai Zhongshan 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, Tianshu Liu, Shanghai Zhongshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06225622
- Sponsor's protocol ID
- CSPC-DEY-CRC-K01
- Status last verified
- Mar 2024
- First submitted
- 15 Jan 2024
- Last updated
- 19 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Escalation and Expansion Clinical Trial of Irinotecan Liposome Combined With Oxaliplatin and 5-FU/LV Plus Bevacizumab as First-line Treatment of Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06225622
- Acronym / sponsor ID
- CSPC-DEY-CRC-K01
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Collaborators
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Study start
- 11 Mar 2024 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 May 2026 (estimated)
- First posted
- 26 Jan 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.
Dose escalation clinical trial: To explore the dose limiting toxicity (DLT) of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab in first-line treatment of patients with advanced metastatic colorectal cancer, and to estimate the maximum tolerated dose (MTD) of combined administration.
Expansion clinical trial: To evaluate the safety and efficacy of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab in first-line treatment of patients with advanced metastatic colorectal cancer. Exploratory analysis of ctDNA changes and genetic mutations in patients at baseline.
Detailed description
This is a dose escalation and expansion study to evaluate the safety and efficacy of irinotecan liposome injection in patients with first-line treatment for metastatic colorectal cancer. In the dose escalation phase, patients will be treated with a combination regimen of irinotecan liposome injection at doses of 60mg/m2, 70mg/m2, and 80mg/m2, and 9 to 18 eligible patients are expected to be enrolled. In the expansion phase, approximately 60 patients will receive combination therapy with irinotecan liposome RP2D dose and exploratory analysis of genetic mutations at baseline and ctDNA changes during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab | Experimental | Drug: Irinotecan Liposome, Drug: Oxaliplatin, Drug: 5-FU, Drug: LV, Drug: Bevacizumab, Drug: CetuximabIn dose escalation study, patients will be treated with irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab. In expansion study, patients will be treated with irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab, depending on their baseline mutation status. Oxaliplatin is accepted up to 12 cycles. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18-75 years old.
- Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma.
- The unresectable stage of metastatic disease has not received any systemic antitumor therapy.
- For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 12 months removed from the date of last administration of neoadjuvant or adjuvant therapy.
- The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria.
Key exclusion criteria (18 listed)
- Patients with known MSI-H or dMMR who were evaluated by investigators as suitable for treatment with immune checkpoint inhibitors.
- Patients allergic to the investigational drug and its excipients.
- Underweight (body mass index [BMI]<18.5 kg/m^2).
- Known or suspected central nervous system metastasis.
- Received irinotecan before enrollment.
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 |
|---|---|---|
| Irinotecan LiposomeIn dose escalation study, irinotecan liposome injection will be administered by an intravenous infusion at three doses of 60 mg/m2, 70 mg/m2 and 80 mg/m2, d1, 14 days per cycle. In expansion study, irinotecan liposome injection will be administered by an intravenous infusion at the dose of RP2D, d1, 14 days per cycle. Until the disease progresses or surgery is possible. | Drug | irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab |
| Oxaliplatin85 mg/m2, intravenously infusion, d1, 14 days per cycle, up to 12 cycles. | Drug | irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab |
| 5-FU2400mg/m2, intravenous infusion, d1-2, 14 days per cycle. Until the disease progresses or surgery is possible. | Drug | irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab |
| LV400mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible. | Drug | irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab |
| Bevacizumab5mg/kg, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.It is used to patients in dose escalation phase and with gene mutation in extension phase. | Drug | irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab |
| Cetuximab500mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.For wild-type patients in extended phase studies. | Drug | irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab |
Primary outcome
Maximum-tolerated dose
Time frame: Up to 14 days
To investigate the safety.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: Start by signing the informed consent form until 4 weeks after the last dose.
To evaluate the incidence and severity of hematological adverse events in patients.
4 secondary outcomes
Objective response rate
Time frame: From initial medication to the date of first documented progression or end of medication, assessed up to 20 months.
Disease control rate
Time frame: From initial medication to the date of first documented progression or end of medication , assessed up to 20 months.
Progression free survival
Time frame: From initial medication to the date of first documented progression or date of death from any cause, whichever came first , assessed up to 22 months.
R0 resection
Time frame: From the first dose to the surgery, assessed up to 22 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2024.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irinotecan Liposome, Oxaliplatin and 5-FU in people with Metastatic Colorectal Cancer, run by Shanghai Zhongshan 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 8 inclusion and 18 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 19 Mar 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 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.
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?
Contact Tianshu Liu, Doctor (+861368 1973 996, liu.tianshu@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum-tolerated dose (time frame: Up to 14 days). 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 19 Mar 2024.