Colorectal Cancer Liver MetastasesPhase 2NCT05588297
Preoperative Nivolumab Plus Bevacizumab Combined With Chemotherapy Before Surgery in Patients With pMMR/MSS Colorectal Cancer Liver Metastases
A Phase 2 study testing CapOx(Capecitabine+ Oxaliplatin), Bevacizumab and Nivolumab in people with Colorectal Cancer Liver Metastases, run by Shanghai Changzheng Hospital.
Trial summary
This prospective, single-arm study aims to investigate the safety and efficacy of Nivolumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS Colorectal cancer liver metastases patients Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer Liver Metastases
- What is being tested?
- CapOx(Capecitabine+ Oxaliplatin), Bevacizumab and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Oct 2022to Oct 2025
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years old and ≤75 years old
- On the basis of data from the literature, we defined liver metastases as B/U if at least one of the following was present: more than four liver metastases, involvement of the hepatic artery or portal vein, or involvement of the biliary duct. A trained radiologist reviewed radiologic images (computed tomography or magnetic resonance imaging scans of the abdomen) taken before the conversion chemotherapy to assess the resectability criteria.
- Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
- Initial diagnosed or recurrent patients will be accepted, patients with recurrence should not have received any treatment include chemotherapy, targeted therapy or immunotherapy within 1 month or radiotherapy within 1 year
- Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
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- Absence of distant metastasis confirmed by CT, MRI or PET/CT
- Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained within 7 days before first dose. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).
- Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.
- Life expectancy> 3 months
- Signed and written informed consent
Who cannot join
- Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
- Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
- Contraindications of bevacizumab
- Hypersensitivity to other monoclonal antibodies.
- Any active, known or suspected autoimmune disease.
- Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
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- History of one of the following diseases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.
- Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
- Active bleeding or abnormal coagulation (aPTT >43s or INR >1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.
- Previously received allogeneic stem cell or parenchymal organ transplantation.
- Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.
- History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
- HIV infection.
- Active hepatitis B or hepatitis C.
- Pregnancy or lactation period, or unwilling to use contraception during the trial.
- With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
- Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
- Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
- Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
- Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
- Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
- Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may contrain the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Safety and Efficacy of Nivolumab Combined With CAPOX Plus Bevacizumab as Neoadjuvant Treatment of pMMR/MSS Colorectal Cancer Liver Metastases Patients：a Single-arm, Phase II, Prospective Study
This prospective, single-arm study aims to investigate the safety and efficacy of Nivolumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS Colorectal cancer liver metastases patients
- Conditions
- Colorectal Cancer Liver Metastases
- Being tested
- CapOx(Capecitabine+ Oxaliplatin), Bevacizumab, Nivolumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapOx(Capecitabine+ Oxaliplatin)Drug
CapOx: Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 4 cycles
BevacizumabDrug
Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles
NivolumabDrug
Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles | Experimental | CapOx: Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 4 cycles;
Bevacizumab：Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles; Nivolumab：Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles; Receives: Drug: CapOx(Capecitabine+ Oxaliplatin); Drug: Bevacizumab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
R0 recession rate
Percentage of patients who achieve R0 resection
Measured: 10 weeks
Pathological complete response rate
Percentage of patients who achieve pathological complete response (pCR) based on local investigator
Measured: 15 weeks
Tumor regression grade (TRG）
Measured: 15 weeks
Secondary outcomes (7)
Objective response rate
Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST).
Measured: Up to 3 years
Event free survival
Measure of time from study treatment to disease progression or death.
Measured: Up to 3 years
Disease-free surviva
Measure of time from the date of surgery to disease relapse or death.
Measured: Up to 3 years
One-year or two-year disease-free survival rate
Percentage of patients who achieve disease-free survival lasting for more than one and two years respectively from the date of surgery.
Measured: Up to 2 years
One-year or two-year overall survival rate
Percentage of patients who achieve survival for more than one and two years respectively from date of first dose.
Measured: Up to 2 years
Incidence of Treatment-Related Adverse Events
Number of adverse events
Measured: Until 30 days after the last treatment
Quality of life score (QoL score）
Assessment of life quality based on EORTC QLQ-C30
Measured: Until 30 days after the last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2022
- Study startOct 2022 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer Liver MetastasesStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05588297
- Sponsor's protocol ID
- ZHOUHAIYANG2
- Status last verified
- Oct 2022
- First submitted
- 18 Oct 2022
- Last updated
- 20 Oct 2022
- 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 20 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Nivolumab Combined With CAPOX Plus Bevacizumab as Neoadjuvant Treatment of pMMR/MSS Colorectal Cancer Liver Metastases Patients：a Single-arm, Phase II, Prospective Study
- ClinicalTrials.gov ID
- NCT05588297
- Acronym / sponsor ID
- ZHOUHAIYANG2
- Conditions
- Colorectal Cancer Liver Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Study start
- Oct 2022 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 20 Oct 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.
This prospective, single-arm study aims to investigate the safety and efficacy of Nivolumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS Colorectal cancer liver metastases patients
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles | Experimental | Drug: CapOx(Capecitabine+ Oxaliplatin), Drug: Bevacizumab, Drug: NivolumabCapOx: Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles; Nivolumab：Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles; |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥18 years old and ≤75 years old
- On the basis of data from the literature, we defined liver metastases as B/U if at least one of the following was present: more than four liver metastases, involvement of the hepatic artery or portal vein, or involvement of the biliary duct. A trained radiologist reviewed radiologic images (computed tomography or magnetic resonance imaging scans of the abdomen) taken before the conversion chemotherapy to assess the resectability criteria.
- Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
- Initial diagnosed or recurrent patients will be accepted, patients with recurrence should not have received any treatment include chemotherapy, targeted therapy or immunotherapy within 1 month or radiotherapy within 1 year
- Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
Key exclusion criteria (22 listed)
- Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
- Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
- Contraindications of bevacizumab
- Hypersensitivity to other monoclonal antibodies.
- Any active, known or suspected autoimmune disease.
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 |
|---|---|---|
| CapOx(Capecitabine+ Oxaliplatin)CapOx: Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 4 cycles | Drug | Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles |
| BevacizumabBevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles | Drug | Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles |
| NivolumabNivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles | Drug | Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles |
Primary outcome
R0 recession rate
Time frame: 10 weeks
Percentage of patients who achieve R0 resection
Pathological complete response rate
Time frame: 15 weeks
Percentage of patients who achieve pathological complete response (pCR) based on local investigator
Tumor regression grade (TRG）
Time frame: 15 weeks
7 secondary outcomes
Objective response rate
Time frame: Up to 3 years
Event free survival
Time frame: Up to 3 years
Disease-free surviva
Time frame: Up to 3 years
One-year or two-year disease-free survival rate
Time frame: Up to 2 years
One-year or two-year overall survival rate
Time frame: Up to 2 years
Incidence of Treatment-Related Adverse Events
Time frame: Until 30 days after the last treatment
Quality of life score (QoL score）
Time frame: Until 30 days after the last treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2022.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CapOx(Capecitabine+ Oxaliplatin), Bevacizumab and Nivolumab in people with Colorectal Cancer Liver Metastases, run by Shanghai Changzheng Hospital.
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 11 inclusion and 22 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 20 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Haiyang Zhou, MD (+86 13764515639, haiyang1985_1@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
R0 recession rate (time frame: 10 weeks). The study lists 3 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 20 Oct 2022.