Colorectal Neoplasms MalignantPhase 2NCT05278351
Tislelizumab Plus Cetuximab and Irinotecan vs Third-line Standard-of-care in Refractory mCRC
A Phase 2 study testing Tislelizumab Combined With Cetuximab and Irinotecan and Third-line regimens in people with Colorectal Neoplasms Malignant, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
This is a multicenter, randomized, controlled, phase II study to evaluate the efficacy and safety of tislelizumab combined with cetuximab and irinotecan（group A） compared to third-line regimens selected by researchers（group B） in the treatment of Ras wild-type recurrent and refractory metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms Malignant
- What is being tested?
- Tislelizumab Combined With Cetuximab and Irinotecan and Third-line regimens
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteChina
- Study dates
- 13 Jul 2022to 1 Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age≥18years；
- The ECOG PS score was≤1;
- Ras wild-type colorectal cancer diagnosed by histology and/or cytology has metastasis or recurrence that cannot be cured by surgery;
- Have received at least second-line systemic anti-tumor treatments for mCRC and failed, in which chemotherapy drugs can include fluorouracil, oxaliplatin or irinotecan; with or without targeted drugs, such as cetuximab or bevacizumab;
- At least one measurable lesion defined according to RECIST version 1.1;
- Patients with fertility must be willing to take efficient contraceptive measures during the study period and ≥ 120 days after the last administration of drugs; female patients have negative urine or serum pregnancy test results ≤ 7 days before the first administration of the study drugs;
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- Fully understand and voluntarily sign the informed consent form;
- Organ function is good ≤ 7 days before randomization, as shown in the following:
- a.Blood transfusion or growth factor support within 2 weeks before enrollment are not allowed to meet the enrollment criteria: i. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9 / L; ii.Platelet count≥ 75 × 10^9 / L; iii.Hemoglobin≥9g/dL or 90g / L or 5.6mmol/l; b. Serum total bilirubin ≤1.5 times the upper limit of normal value(ULN); c. Aspartate aminotransferase (AST) and alanine aminotransferase(ALT) ≤2.5 times ULN, or ALT and/or AST ≤5 times ULN in patients with liver metastasis; d. Serum creatinine ≤ 1.5 times the upper limit of normal value(ULN); e. Partial prothrombin time (APTT) or prothrombin time (PT) ≤1.5 times ULN; f. Albumin ≥30g / L;
Who cannot join
- Any previous histological or hematological ctDNA test showed mismatch repair gene deletion (dMMR), microsatellite instability (MSI-H), BRAF mutant patients;
- Previous immunotherapy, including anti-PD-1, anti-PD-L1, anti-CTLA-4 or any cellular immunotherapy;
- There is active leptomeningeal disease or brain metastasis that is not well controlled;
- History of active autoimmune diseases or autoimmune diseases that may recur. Note: Patients with the following diseases are not excluded and can be further screened:
- Well controlled type I diabetes mellitus
- Hypothyroidism (controlled by hormone replacement therapy only)
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- Well controlled celiac disease
- Skin diseases that do not require systematic treatment (e.g. vitiligo, psoriasis, hair loss)
- Any other disease that is not expected to recur without external triggers
- Any active malignant tumor ≤ 5 years before the first administration of the study drug, except the specific cancer studied in this trial and any locally recurrent cancer that has received radical treatment (such as excised basal cell or squamous cell skin cancer, cervical or breast cancer in situ);
- Any case requiring systemic treatment with corticosteroids (prednisone or equivalent > 10 mg / day) or other immunosuppressive drugs ≤ 14 days before the first administration of the study drug. Note: patients who have currently or previously used any of the following steroid regimens are not excluded:
- Adrenal replacement steroids (prednisone or equivalent ≤ 10 mg / day)
- Inhaled corticosteroids with very low local, eye, intra-articular, intranasal or systemic absorption
- Short term (≤ 7 days) prophylactic use of corticosteroids (e.g. for the treatment of contrast medium allergy) or for the treatment of non autoimmune diseases (e.g. delayed type hypersensitivity caused by contact allergens)
- There was uncontrolled diabetes, or over 3 grade hypoalbuminemia or >1 grade potassium, sodium or calcium abnormalities within 14 days before the first drug administration,
- History of interstitial lung disease, non infectious pneumonia or uncontrolled diseases, including pulmonary fibrosis, acute lung disease, etc;
- Urine routine examination showed that urinary protein was ≥ + +, and 24-hour urinary protein was > 1.0 g;
- Severe chronic or active infections (including tuberculosis infection) requiring systemic antibacterial, antifungal or antiviral treatment within 14 days before the first administration of the study drug note: Patients with viral hepatitis are allowed to receive antiviral treatment;
- Active mental system diseases (schizophrenia, severe depressive disorder, bipolar disorder, etc.). Depression being treated with antidepressants is not an exclusion criterion;
- Known history of human immunodeficiency virus (HIV) infection;
- Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500 IU / ml) or active HCV carriers with detectable HCV RNA. Note: carriers of inactive hepatitis B surface antigen (HBsAg) and patients with stable hepatitis B (HBV DNA < 500 IU / ml) can be included in the group;
- Any major surgery requiring general anesthesia ≤ 28 days before the first administration of the study drug;
- Previous heterologous stem cell transplantation or organ transplantation;
- Any of the following cardiovascular criteria
- Cardiogenic chest pain ≤ 28 days before the first administration of the study drug was defined as moderate pain limiting the movement of daily living instruments
- Symptomatic pulmonary embolism ≤ 28 days before the first administration of the study drug
- There was any history of acute myocardial infarction ≤ 6 months before the first administration of the study drug
- There was any history of heart failure with NYHA grade III or IV (6) ≤ 6 months before the first administration of the study drug
- There were any ventricular arrhythmia events with severity ≥ 2 ≤ 6 months before the first administration of the study drug
- There was any history of cerebrovascular accident ≤ 6 months before the first administration of the study drug
- Left ventricular ejection fraction (LVEF) ≤ lower normal limit (LLN) assessed by multi gated acquisition (MUGA) scan or echocardiography (echo). Follow up assessments must be performed in the same way as the baseline assessment
- Any syncope or seizure occurring ≤ 28 days before the first administration of the study drug
- Hypertension with poor control after multiple drug treatment (defined as systolic blood pressure > 140 mmHg and / or diastolic blood pressure > 90 mmHg);
- Hypersensitivity to any component of the study drug or control drug or to any component of the container;
- Bleeding, thrombotic disease or use of anticoagulants (such as warfarin) or similar drugs requiring therapeutic INR monitoring within 6 months before the first administration of the study drug;
- Chemotherapy, targeted therapy, immunotherapy (e.g. interleukin, interferon, thymosin, etc.), hormone therapy or any study therapy were performed within 14 days of the first administration of the study drug or within 5 half lives, whichever is shorter;
- Any Chinese herbal medicine or proprietary Chinese medicine with anticancer activity approved by China National Drug Administration within 14 days before the first administration of the study drug (regardless of cancer type);
- Toxicity from previous anticancer treatments did not improve to baseline or stable, except for AEs that were not considered as safety risks (e.g., hair loss, neuropathy and specific laboratory abnormalities);
- Live vaccine was administered ≤ 28 days before the first administration of the study drug.
- Potential disease conditions (including laboratory abnormalities), alcohol or drug abuse or dependence, which are not conducive to the administration of the study drug or affect the interpretation of the toxicity and AE of the study drug, or lead to insufficient or reduced compliance with the study;
- Participate in another clinical study at the same time, unless it is an observational (non intervention) clinical study or is in the follow-up period of intervention study;
- Inability to swallow capsules or diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, total gastrectomy or small bowel resection, weight loss surgery, inflammatory bowel disease or incomplete or complete intestinal obstruction;
- Uncontrollable pleural effusion, pericardial effusion or peritoneal effusion requiring frequent drainage or medical intervention within 7 days of the first administration of the study drug (clinically significant recurrence, additional intervention is required within 2 weeks after the intervention, excluding exfoliative cytology of the exudate);
- Pregnant or lactating women.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Zhongshan Hospital
Shanghai, Shanghai Municipality, 200032
tianshu liu, +8613681973996, xxjqd@126.com
About this study
Official title: Tislelizumab Plus Cetuximab and Irinotecan Comparing the Third-line Standard-of-care Selected by Researchers in the Treatment of Ras Wild-type Recurrent Refractory Metastatic Colorectal Cancer: A Multicenter, Randomized, Controlled Clinical Trial
This is a multicenter, randomized, controlled, phase II study to evaluate the efficacy and safety of tislelizumab combined with cetuximab and irinotecan（group A） compared to third-line regimens selected by researchers（group B） in the treatment of Ras wild-type recurrent and refractory metastatic colorectal cancer. This study will include Ras wild-type colorectal cancer that failed at least second-line treatment inthe past, including chemotherapy (oxaliplatin, irinotecan, fluorouracil) with or without targeted drugs (cetuximab, bevacizumab). 87 patients will be randomly assigned to group A and group B according to 2:1. The enrollment time is expected to be 12 months and the follow-up is expected to be 24 months.
- Conditions
- Colorectal Neoplasms Malignant
- Being tested
- Tislelizumab Combined With Cetuximab and Irinotecan, Third-line regimens
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab Combined With Cetuximab and IrinotecanDrug
Also called TEC
Tislelizumab (an anti-PD-1 monoclonal antibody) Cetuximab (monoclonal antibody against EGFR) Irinotecan
Third-line regimensDrug
Trifluridinetipiracil or Regorafenib or Fruquintinib
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Tislelizumab 200mg, D1, D15, intravenous drip, Q4W and Cetuximab 500mg/m2, D1, D15, intravenous drip, Q4W and Irinotecan 180mg/m2, D1, D15, intravenous drip, Q4W Receives: Drug: Tislelizumab Combined With Cetuximab and Irinotecan |
| B | Active comparator | Fruquinitinib 5mg QD D1-21, oral, Q4W or Regorafenib 160mg QD D1-21 oral, Q4W or Trifluridine Tipiracil Tablets 35mg/m2 BID D1-D5, D8-D12 oral, Q4W Receives: Drug: Third-line regimens |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival time (PFS)
time from the start of medication to the initial progression of the disease
Measured: 24 months after the last subject participating in
Secondary outcomes (3)
Objective response rate (ORR)
proportion of patients with complete and partial remission in the best efficacy
Measured: 24 months after the last subject participating in
Disease control rate (DCR)
the best efficacy is the proportion of patients with complete remission, partial remission and stable disease
Measured: 24 months after the last subject participating in
Overall survival (OS)
time from the start of medication to death
Measured: 36 months after the last subject participating in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2022
- Study start13 Jul 2022
- Primary completion1 Apr 2024 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Neoplasms MalignantStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 87 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tianshu Liu, Shanghai Zhongshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05278351
- Sponsor's protocol ID
- TEC2
- Status last verified
- Mar 2023
- First submitted
- 8 Mar 2022
- Last updated
- 31 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tislelizumab Plus Cetuximab and Irinotecan Comparing the Third-line Standard-of-care Selected by Researchers in the Treatment of Ras Wild-type Recurrent Refractory Metastatic Colorectal Cancer: A Multicenter, Randomized, Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT05278351
- Acronym / sponsor ID
- TEC2
- Conditions
- Colorectal Neoplasms Malignant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 87 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 13 Jul 2022 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 14 Mar 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 is a multicenter, randomized, controlled, phase II study to evaluate the efficacy and safety of tislelizumab combined with cetuximab and irinotecan（group A） compared to third-line regimens selected by researchers（group B） in the treatment of Ras wild-type recurrent and refractory metastatic colorectal cancer. This study will include Ras wild-type colorectal cancer that failed at least second-line treatment inthe past, including chemotherapy (oxaliplatin, irinotecan, fluorouracil) with or without targeted drugs (cetuximab, bevacizumab). 87 patients will be randomly assigned to group A and group B according to 2:1. The enrollment time is expected to be 12 months and the follow-up is expected to be 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Tislelizumab Combined With Cetuximab and IrinotecanTislelizumab 200mg, D1, D15, intravenous drip, Q4W and Cetuximab 500mg/m2, D1, D15, intravenous drip, Q4W and Irinotecan 180mg/m2, D1, D15, intravenous drip, Q4W |
| B | Active comparator | Drug: Third-line regimensFruquinitinib 5mg QD D1-21, oral, Q4W or Regorafenib 160mg QD D1-21 oral, Q4W or Trifluridine Tipiracil Tablets 35mg/m2 BID D1-D5, D8-D12 oral, Q4W |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age≥18years；
- The ECOG PS score was≤1;
- Ras wild-type colorectal cancer diagnosed by histology and/or cytology has metastasis or recurrence that cannot be cured by surgery;
- Have received at least second-line systemic anti-tumor treatments for mCRC and failed, in which chemotherapy drugs can include fluorouracil, oxaliplatin or irinotecan; with or without targeted drugs, such as cetuximab or bevacizumab;
- At least one measurable lesion defined according to RECIST version 1.1;
Key exclusion criteria (44 listed)
- Any previous histological or hematological ctDNA test showed mismatch repair gene deletion (dMMR), microsatellite instability (MSI-H), BRAF mutant patients;
- Previous immunotherapy, including anti-PD-1, anti-PD-L1, anti-CTLA-4 or any cellular immunotherapy;
- There is active leptomeningeal disease or brain metastasis that is not well controlled;
- History of active autoimmune diseases or autoimmune diseases that may recur. Note: Patients with the following diseases are not excluded and can be further screened:
- Any active malignant tumor ≤ 5 years before the first administration of the study drug, except the specific cancer studied in this trial and any locally recurrent cancer that has received radical treatment (such as excised basal cell or squamous cell skin cancer, cervical or breast cancer in situ);
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 |
|---|---|---|
| Tislelizumab Combined With Cetuximab and IrinotecanAlso: TECTislelizumab (an anti-PD-1 monoclonal antibody) Cetuximab (monoclonal antibody against EGFR) Irinotecan | Drug | A |
| Third-line regimensTrifluridinetipiracil or Regorafenib or Fruquintinib | Drug | B |
Primary outcome
Progression free survival time (PFS)
Time frame: 24 months after the last subject participating in
time from the start of medication to the initial progression of the disease
3 secondary outcomes
Objective response rate (ORR)
Time frame: 24 months after the last subject participating in
Disease control rate (DCR)
Time frame: 24 months after the last subject participating in
Overall survival (OS)
Time frame: 36 months after the last subject participating in
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Individual participant dataSharing planned: Yes
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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 2 study testing Tislelizumab Combined With Cetuximab and Irinotecan and Third-line regimens in people with Colorectal Neoplasms Malignant, 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 9 inclusion and 44 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 31 Mar 2023. 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?
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?
Progression free survival time (PFS) (time frame: 24 months after the last subject participating in). 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 31 Mar 2023.