Metastatic Colorectal CancerPhase 2NCT05229003
Irinotecan Plus Anlotinib or Further in Combination With Penpulimab for Second-line Treatment of mCRC
A Phase 2 study testing Anlotinib, Penpulimab and Irinotecan in people with Metastatic Colorectal Cancer, run by Fudan University at 1 site in China.
Trial summary
This is an exploratory, non-controlled, multi-cohort, phase II small-sample clinical study designed to evaluate the clinical benefit of second-line treatment with anlotinib plus irinotecan or further in combination with a PD-1 monoclonal antibody (penpulimab) in patients with advanced colorectal cancer after… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Anlotinib, Penpulimab and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteChina
- Study dates
- 9 Mar 2022to 31 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recurrent/metastatic colorectal adenocarcinoma confirmed by histopathological pathology report;
- The patient received oxaliplatin in combination with fluorouracil as the first-line systemic therapy (with or without anti-EGFR mab or VEGF mab) and failed. Fluorouracil (5-FU, capecitabine, or S-1) and oxaliplatin must be included in the first-line regimens. Treatment failure was defined as: disease progression or intolerable toxicity occurred during treatment or within 3 months after the last treatment; Note: Early adjuvant/neoadjuvant therapy is permitted. If recurrence or metastasis occurs during adjuvant/neoadjuvant therapy or within 6 months after completion, adjuvant/neoadjuvant therapy is considered a failure of first-line chemotherapy for advanced disease;
- With one or more measurable lesions, the longest diameter measured by spiral CT scan should be at least 10 mm, and the longest diameter measured by conventional CT scan should be at least 20 mm (RECIST standard, version 1.1);
- the type of KRAS, NRAS, BRAF, and MSI were known, requiring wild type of BRAF. Cohort A required patients with MSS/pMMR status.
- ECOG score was 0-1;
- Life expectancy ≥12 weeks;
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- The patient has recovered from damage caused by other anti-tumor therapy, received cytotoxic drugs, radiotherapy or surgery for ≥4 weeks, and the wound has completely healed;
- Bone marrow capacity and liver and kidney function were sufficiently reserved within 7 days before screening: absolute neutrophil (ANC) count ≥1.5x109 /L; Hemoglobin ≥ 8.0g/ dL; Platelet count ≥80 x109 /L; Total bilirubin < 1.5 times upper normal limit (ULN); ALT and AST< 2.5x ULN (with liver metastasis <5x ULN); Serum creatinine ≤1 x ULN, the clearance rate of endogenous creatinine >50ml/min;
- Women of childbearing age should take effective contraceptive measures;
- Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.
Who cannot join
- A history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
- Patients with hypertension that could not be controlled by antihypertensive medication (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg), coronary heart disease of grade I or above, arrhythmia of grade I or above (including prolonged QTc interval > 450ms in males and > 470 ms in females) and cardiac dysfunction of grade I or above;
- Symptomatic brain or meningeal metastases (unless the patient was treated for >6 months, imaging results were negative within 4 weeks prior to study entry, and tumor-related clinical symptoms were stable at study entry); with a history of uncontrolled epileptic seizures, central nervous system dysfunction, or mental disorders;
- Uncontrolled pleural or abdominal effusion;
- Undergoing kidney dialysis;
- severe or uncontrolled infection;
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- pregnant or lactating women who are fertile but have not taken adequate contraceptive measures;
- Multiple factors affecting oral medication (inability to swallow, chronic diarrhea and intestinal obstruction);
- Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg< 2G /L), bleeding tendency or receiving thrombolytic or anticoagulant treatment; patients with gastrointestinal bleeding risk should not be enrolled, including the following conditions :(1) active peptic ulcer lesions and fecal occult blood (++); (2) patients with history of black stools and hematemesis within 3 months;
- Prior exposure to any anti-PD-1 or anti-PD-L1, PD-L2, CD137, CTLA-4 antibody therapy, or any other antibody or drug that specifically targets T-cell costimulation or immune checkpoint pathways.
- Former treatment of irinotecan for 1 or more cycles;
- Prior exposure to any anti-VEGFR small molecule inhibitors (e.g. Apatinib, regorafenib, Fruquintinib, Anlotinib, etc.)
- Participated in clinical trials of other drugs within four weeks
- Urine routine examination indicated urine protein > 2+, or 24-hour urine protein quantification ≥1.0g/24h
- Use of immunosuppressive agents within 4 weeks prior to the first dose of study therapy, excluding nasal, inhaled, or other topical or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/ d of prednisone or equivalent doses of other glucocorticoids), or hormone use for the prevention of contrast agent allergy.
- Residual liver volume is less than 50% of the total liver volume. -
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Chenchen Wang, MD, +8613774232040, wccnancy2003@aliyun.com
Weijian Guo, MD,PhD
About this study
Official title: A Randomized, Uncontrolled, Exploratory Phase 2 Trial of Irinotecan Plus Anlotinib or Further in Combination With Penpulimab as Second-line Treatment of Metastatic Colorectal Cancer (ZL-IRIAN)
This is an exploratory, non-controlled, multi-cohort, phase II small-sample clinical study designed to evaluate the clinical benefit of second-line treatment with anlotinib plus irinotecan or further in combination with a PD-1 monoclonal antibody (penpulimab) in patients with advanced colorectal cancer after first-line treatment failure. To explore the rationality of the combination of chemotherapy and targeted therapy and immunotherapy strategy and obtain relevant survival and safety data. The study will fully evaluate the efficacy, PFS, OS, safety and related biomarkers of the regimen.
Read the detailed description
The design of this study is an open, non-controlled, multi-cohort, phase II, small-sample prospective clinical study, including eligible patients with metastatic colorectal cancer who received the second-line treatment, and two cohort were included, Cohort A received anlotinib and irinotecan chemotherapy (n=23), and the treatment of cohort B consisted of anlotinib and anti-PD-1 mab (penpulimab) plus irinotecan chemotherapy. Patients were firstly enrolled in cohort A, and if patients in cohort A achieved an response rate of no less than 15% (i.e., no less than 4 out of 23 patients receiving efficacy evaluation achieved CR/PR), the following patients would be enrolled in cohort B. If the response rate of patients in cohort A was less than 15%, subsequent cohort B enrollment (non-control) would be stopped.
A total of 46 patients enrolled in this study, actually.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Anlotinib, Penpulimab, Irinotecan
- Keywords
- metastatic colorectal cancer, second-line treatment, target therapy, enlotinib, penpulimab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Anlotinib 8mg or 10mg, d1-9，q2w
PenpulimabDrug
Penpulimab 200mg, d6, q2w
IrinotecanDrug
Irinotecan 180mg/m2, d6, q2w
| Study group | Role | What they receive |
|---|---|---|
| cohort A | Experimental | Anlotinib + Irinotecan:
Anlotinib, 10mg, oral, once daily, D1-10, q2W; Irinotecan, 180mg/m2, iv drip, d6, q2w. Receives: Drug: Anlotinib; Drug: Irinotecan |
| cohort B | Experimental | Anlotinib + Penpulimab + Irinotecan:
Anlotinib, 8mg, oral, once daily, d1-10, q2w; Penpulimab 200mg, i.v. d6, q2w; Irinotecan, 180mg/m2, iv infusion, d6, q2w. Receives: Drug: Anlotinib; Drug: Penpulimab; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
objective response rate
Measured: the rate of patients with CR and PR, through study completion, an average of 1 year
Secondary outcomes (5)
PFS
progression free survival
Measured: from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
OS
overall survival
Measured: from the time signing of ICF until the date of death from any cause, assessed up to 36 months
DoR
duration of response
Measured: the time between the first tumor evaluation for CR or PR and the first evaluation for PD(Progressive Disease) or death from any cause, assessed up to 36 months
DCR
disease control rate
Measured: the rate of patients with CR, PR and SD, through study completion, an average of 1 year
AEs
the adverse events of all enrolled patients
Measured: the adverse events rate and types of all enrolled patients, through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2022
- Study start9 Mar 2022
- Primary completion31 May 2025 (estimated)
- Study completion31 Dec 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 Fudan UniversityThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients were first enrolled into cohort A, and when the efficacy of cohort A reached a certain percentage, the enrollment of cohort B started then.
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Weijian Guo, Fudan University
- Investigators
- Weijian Guo, M.D, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05229003
- Sponsor's protocol ID
- ZL-IRIAN
- Status last verified
- Jul 2024
- First submitted
- 25 Jan 2022
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Uncontrolled, Exploratory Phase 2 Trial of Irinotecan Plus Anlotinib or Further in Combination With Penpulimab as Second-line Treatment of Metastatic Colorectal Cancer (ZL-IRIAN)
- ClinicalTrials.gov ID
- NCT05229003
- Acronym / sponsor ID
- ZL-IRIAN
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- metastatic colorectal cancer, second-line treatment, target therapy, enlotinib, penpulimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 9 Mar 2022 (actual)
- Primary completion
- 31 May 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 8 Feb 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 an exploratory, non-controlled, multi-cohort, phase II small-sample clinical study designed to evaluate the clinical benefit of second-line treatment with anlotinib plus irinotecan or further in combination with a PD-1 monoclonal antibody (penpulimab) in patients with advanced colorectal cancer after first-line treatment failure. To explore the rationality of the combination of chemotherapy and targeted therapy and immunotherapy strategy and obtain relevant survival and safety data. The study will fully evaluate the efficacy, PFS, OS, safety and related biomarkers of the regimen.
Detailed description
The design of this study is an open, non-controlled, multi-cohort, phase II, small-sample prospective clinical study, including eligible patients with metastatic colorectal cancer who received the second-line treatment, and two cohort were included, Cohort A received anlotinib and irinotecan chemotherapy (n=23), and the treatment of cohort B consisted of anlotinib and anti-PD-1 mab (penpulimab) plus irinotecan chemotherapy. Patients were firstly enrolled in cohort A, and if patients in cohort A achieved an response rate of no less than 15% (i.e., no less than 4 out of 23 patients receiving efficacy evaluation achieved CR/PR), the following patients would be enrolled in cohort B. If the response rate of patients in cohort A was less than 15%, subsequent cohort B enrollment (non-control) would be stopped.
A total of 46 patients enrolled in this study, actually.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients were first enrolled into cohort A, and when the efficacy of cohort A reached a certain percentage, the enrollment of cohort B started then.
| Arm | Type | Receives |
|---|---|---|
| cohort A | Experimental | Drug: Anlotinib, Drug: IrinotecanAnlotinib + Irinotecan: Anlotinib, 10mg, oral, once daily, D1-10, q2W; Irinotecan, 180mg/m2, iv drip, d6, q2w. |
| cohort B | Experimental | Drug: Anlotinib, Drug: Penpulimab, Drug: IrinotecanAnlotinib + Penpulimab + Irinotecan: Anlotinib, 8mg, oral, once daily, d1-10, q2w; Penpulimab 200mg, i.v. d6, q2w; Irinotecan, 180mg/m2, iv infusion, d6, q2w. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Recurrent/metastatic colorectal adenocarcinoma confirmed by histopathological pathology report;
- The patient received oxaliplatin in combination with fluorouracil as the first-line systemic therapy (with or without anti-EGFR mab or VEGF mab) and failed. Fluorouracil (5-FU, capecitabine, or S-1) and oxaliplatin must be included in the first-line regimens. Treatment failure was defined as: disease progression or intolerable toxicity occurred during treatment or within 3 months after the last treatment; Note: Early adjuvant/neoadjuvant therapy is permitted. If recurrence or metastasis occurs during adjuvant/neoadjuvant therapy or within 6 months after completion, adjuvant/neoadjuvant therapy is considered a failure of first-line chemotherapy for advanced disease;
- With one or more measurable lesions, the longest diameter measured by spiral CT scan should be at least 10 mm, and the longest diameter measured by conventional CT scan should be at least 20 mm (RECIST standard, version 1.1);
- the type of KRAS, NRAS, BRAF, and MSI were known, requiring wild type of BRAF. Cohort A required patients with MSS/pMMR status.
- ECOG score was 0-1;
Key exclusion criteria (16 listed)
- A history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
- Patients with hypertension that could not be controlled by antihypertensive medication (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg), coronary heart disease of grade I or above, arrhythmia of grade I or above (including prolonged QTc interval > 450ms in males and > 470 ms in females) and cardiac dysfunction of grade I or above;
- Symptomatic brain or meningeal metastases (unless the patient was treated for >6 months, imaging results were negative within 4 weeks prior to study entry, and tumor-related clinical symptoms were stable at study entry); with a history of uncontrolled epileptic seizures, central nervous system dysfunction, or mental disorders;
- Uncontrolled pleural or abdominal effusion;
- Undergoing kidney dialysis;
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 |
|---|---|---|
| AnlotinibAnlotinib 8mg or 10mg, d1-9，q2w | Drug | cohort A, cohort B |
| PenpulimabPenpulimab 200mg, d6, q2w | Drug | cohort B |
| IrinotecanIrinotecan 180mg/m2, d6, q2w | Drug | cohort A, cohort B |
Primary outcome
ORR
Time frame: the rate of patients with CR and PR, through study completion, an average of 1 year
objective response rate
5 secondary outcomes
PFS
Time frame: from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
OS
Time frame: from the time signing of ICF until the date of death from any cause, assessed up to 36 months
DoR
Time frame: the time between the first tumor evaluation for CR or PR and the first evaluation for PD(Progressive Disease) or death from any cause, assessed up to 36 months
DCR
Time frame: the rate of patients with CR, PR and SD, through study completion, an average of 1 year
AEs
Time frame: the adverse events rate and types of all enrolled patients, through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
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CRC
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.
Weijian Guo, M.D principal investigator
Fudan University
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 Anlotinib, Penpulimab and Irinotecan in people with Metastatic Colorectal Cancer, run by Fudan University 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 16 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 3 Jul 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chenchen Wang, M.D (+8613774232040, wccnancy2003@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: the rate of patients with CR and PR, through study completion, an average of 1 year). 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 3 Jul 2024.