Advanced Colorectal CancerPhase 1/2NCT05035914
Anlotinib Combined With mXELIRI as Second-line Treatment of Advanced Colorectal Cancer
A Phase 1/2 study testing Anlotinib Hydrochloride in people with Advanced Colorectal Cancer, run by Guangzhou University of Traditional Chinese Medicine at 1 site in China.
Trial summary
1. Determine the maximum tolerable dose (MTD) and / or phase II recommended dose (RP2D) of the allotinib combined mXELIRI protocol. 2. To evaluate the safety and tolerance of the combination of anlotinib and mXELIRI in the second-line treatment of patients with advanced colorectal cancer Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Colorectal Cancer
- What is being tested?
- Anlotinib Hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteChina
- Study dates
- 9 Jul 2021to 31 Dec 2024
- Phase
- Phase 1/2
- 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
- ECOG performance status (PS) 0-1
- The expected survival time is not less than 12 weeks
- Patients with stage IV colorectal cancer confirmed by pathology or imaging have measurable lesions (according to RECIST 1.1, the long diameter of tumor lesions on CT scan is greater than or equal to 10 mm, the short diameter of lymph node lesions on CT scan is greater than or equal to 15 mm, and the measurable lesions have not received radiotherapy, freezing and other local treatment);
- First line patients with advanced or intolerant colorectal cancer treated with bevacizumab combined with oxaliplatin (FOLFOX or capeox, etc.);
- The function of main organs was normal (in accordance with the chemotherapy standard);
- Women of childbearing age must have taken reliable contraceptive measures or conducted pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they are willing to use appropriate contraceptive methods during the test period and 8 weeks after the last administration of the test drug. For men, it is necessary to agree to use appropriate contraceptive methods or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug;
- The subjects volunteered to join the study and signed informed consent, with good compliance and follow-up.
Who cannot join
- The histological type was mucinous adenocarcinoma or ovarian implant metastasis;
- First line patients with irinotecan treatment;
- Patients who had been treated with anlotinib hydrochloride capsules in the past;
- Symptomatic brain metastases (patients with stable symptoms and completed treatment 21 days before enrollment can be enrolled, but no cerebral hemorrhage symptoms should be confirmed by brain MRI, CT or venography evaluation);
- Patients with hypertension who could not be well controlled by single antihypertensive drug treatment (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg); Or use two or more antihypertensive drugs to control blood pressure
- The patient also had more than 1 degree of adverse reactions (except hair loss, neurotoxicity more than 2 degrees) which could not be alleviated due to previous treatment;
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- They have the following cardiovascular diseases: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including QTc interval ≥ 450 ms for male and ≥ 470 MS for female); According to NYHA criteria, grade Ⅲ - Ⅳ cardiac insufficiency, or left ventricular ejection fraction (LVEF) < 50% by echocardiography;
- Abnormal coagulation function (INR > 1.5 or PT > ULN + 4 seconds or APTT > 1.5 ULN), bleeding tendency or receiving thrombolysis or anticoagulation therapy;
- There were significant clinical bleeding symptoms or clear bleeding tendency in the first 3 months, such as gastrointestinal bleeding, hemorrhagic hemorrhoids, hemorrhagic gastric ulcer, baseline fecal occult blood + + or above, or vasculitis;
- Arteriovenous thrombotic events occurred in the first 12 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism;
- Known hereditary or acquired bleeding and thrombotic tendency (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.);
- Wound or fracture that has not been cured for a long time (pathological fracture caused by tumor is not included);
- Patients in the study group had undergone major surgery or severe traumatic injury, fracture or ulcer within 4 weeks;
- There are obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
- Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before admission;
- Urine routine showed that urine protein was ≥ + +, and 24-hour urine protein was more than or equal to 1.0 G;
- Serous effusion (including pleural effusion, ascites and pericardial effusion) with clinical symptoms and requiring symptomatic treatment;
- Asymptomatic serous effusion can be included in the group, symptomatic serous effusion after active symptomatic treatment (can not use anticancer drugs for serous effusion treatment), patients who can be included in the group after the judgment of the researchers are allowed to be included in the group.
- Active infections need antimicrobial treatment (for example, the use of antibiotics and antiviral drugs, excluding chronic hepatitis B anti hepatitis B treatment, antifungal treatment).
- There was active hepatitis B (HBV DNA > 2000IU/mL or 104 copy number /mL) or hepatitis C (hepatitis B antibody positive, and HCV RNA was higher than the lower limit of analysis).
- Those who have a history of psychotropic drug abuse and can not give up or have mental disorders;
- Those who participated in clinical trials of other anti-tumor drugs within 4 weeks before enrollment;
- Previous or other untreated malignancies were cured except for basal cell carcinoma, cervical carcinoma in situ and superficial bladder cancer.
- Those who received strong CYP3A4 inhibitor treatment within 7 days before randomization, or those who received strong CYP3A4 inducer treatment within 12 days before participating in the study;
- Pregnant or lactating women; Patients with fertility are unwilling or unable to take effective contraceptive measures;
- The researcher judges other situations that may affect the clinical research and the judgment of research results.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guangdong Provincial Hospital of Chinese Medicine
Guangzhou, Guangdong, 510120
Lirong Liu, MM, 86 20 81887233 ext. 34830, doctorllr@163.com
Haibo Zhang, Professor
About this study
Official title: Phase Ib / II Study of Anlotinib Combined With mXELIRI as Second-line Treatment of Advanced Colorectal Cancer
- Determine the maximum tolerable dose (MTD) and / or phase II recommended dose (RP2D) of the allotinib combined mXELIRI protocol.
- To evaluate the safety and tolerance of the combination of anlotinib and mXELIRI in the second-line treatment of patients with advanced colorectal cancer
Read the detailed description
This study consists of two phases, the dose-escalation phase, and the expansion phase. 9-12 patients with advanced colorectal cancer will be included in the dose escalation study. Patients who met the inclusion criteria would be treated with anlotinib QD for 2 weeks, and then stopped for 1 week, combined with mXELIRI. Every 21 days was a treatment cycle. Safety information was collected until the disease progression or intolerable toxicity, so as to determine the MTD and / or RP2D of anlotinib combined with irinotecan in patients with advanced colorectal cancer. The study adopted the traditional 3+3 design .
The primary outcome in dose-expansion phase was objective response rate(ORR).
- Conditions
- Advanced Colorectal Cancer
- Being tested
- Anlotinib Hydrochloride
- Keywords
- advanced colorectal cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anlotinib HydrochlorideDrug
Anlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once daily, 2 weeks on/1 week off.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: anlotinib+mXELIRI | Experimental | Dose-escalation phase:
A: anlotinib 8 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle;
B: anlotinib 10 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle;
C: anlotinib 12 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle;
Dose-expansion phase:
anlotinib RP2D, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; Receives: Drug: Anlotinib Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
The main side effects of drugs are the main reasons for limiting the increase of the dose of chemotherapy drugs, which are dose limiting toxicity of chemotherapy drugs
Measured: Through study completion, up to 24 months
Phase II clinical recommended dose (RP2D)
When the minimum number of patients is included in the dose increasing phase, the recommended dose of phase 2 can be determined accurately and quickly
Measured: each 42 days up to intolerance the toxicity or PD
Objective response rate
Objective response rate is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Measured: Through study completion, up to 24 months
Secondary outcomes (5)
Progression free survival
Progress free survival defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause
Measured: From date of enrollment until the date of first documented progression, assessed up to 24 months
Overall survival
Overall survival is defined as the time until death due to any cause
Measured: From date of enrollment until death, assessed up to 24 months
Disease control rate
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1
Measured: Through study completion, up to 24 months
Duration of remission
The time from the first time that CR or PR (no matter which one is measured first) is measured to the first time that disease recurrence or progression is truly recorded
Measured: Through study completion, up to 24 months
Score of quality of Life
The changes of clinical symptoms and objective examination results of tumor patients before and after treatment were observed and scored. According to the requirements of quality of life scale, the scoring results of each field of the scale were recorded in ECRF
Measured: From date of enrollment until death, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start9 Jul 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Colorectal CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou University of Traditional Chinese Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Guangdong Provincial Hospital of Traditional Chinese Medicine
- Responsible party
- Sponsor
- Investigators
- Haibo Zhang, Professor, Principal investigator, Guangdong Provincial Hospital of Traditional Chinese Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05035914
- Sponsor's protocol ID
- Guangzhouucm
- Status last verified
- Sep 2021
- First submitted
- 3 Sep 2021
- Last updated
- 5 Sep 2021
- 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 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib / II Study of Anlotinib Combined With mXELIRI as Second-line Treatment of Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05035914
- Acronym / sponsor ID
- Guangzhouucm
- Conditions
- Advanced Colorectal Cancer
- Keywords
- advanced colorectal cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- Guangzhou University of Traditional Chinese MedicineUniversity, hospital or other
- Collaborators
- Guangdong Provincial Hospital of Traditional Chinese Medicine
- Study start
- 9 Jul 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 5 Sep 2021 (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.
- Determine the maximum tolerable dose (MTD) and / or phase II recommended dose (RP2D) of the allotinib combined mXELIRI protocol.
- To evaluate the safety and tolerance of the combination of anlotinib and mXELIRI in the second-line treatment of patients with advanced colorectal cancer
Detailed description
This study consists of two phases, the dose-escalation phase, and the expansion phase. 9-12 patients with advanced colorectal cancer will be included in the dose escalation study. Patients who met the inclusion criteria would be treated with anlotinib QD for 2 weeks, and then stopped for 1 week, combined with mXELIRI. Every 21 days was a treatment cycle. Safety information was collected until the disease progression or intolerable toxicity, so as to determine the MTD and / or RP2D of anlotinib combined with irinotecan in patients with advanced colorectal cancer. The study adopted the traditional 3+3 design .
The primary outcome in dose-expansion phase was objective response rate(ORR).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: anlotinib+mXELIRI | Experimental | Drug: Anlotinib HydrochlorideDose-escalation phase: A: anlotinib 8 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; B: anlotinib 10 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; C: anlotinib 12 mg, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; Dose-expansion phase: anlotinib RP2D, po, qd, d1-14; iritecan 180-200mg/m2, iv, d1;capecitabine 800mg/m2, po, bid, d1-14; every 3 weeks as a cycle; |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ECOG performance status (PS) 0-1
- The expected survival time is not less than 12 weeks
- Patients with stage IV colorectal cancer confirmed by pathology or imaging have measurable lesions (according to RECIST 1.1, the long diameter of tumor lesions on CT scan is greater than or equal to 10 mm, the short diameter of lymph node lesions on CT scan is greater than or equal to 15 mm, and the measurable lesions have not received radiotherapy, freezing and other local treatment);
- First line patients with advanced or intolerant colorectal cancer treated with bevacizumab combined with oxaliplatin (FOLFOX or capeox, etc.);
- The function of main organs was normal (in accordance with the chemotherapy standard);
Key exclusion criteria (26 listed)
- The histological type was mucinous adenocarcinoma or ovarian implant metastasis;
- First line patients with irinotecan treatment;
- Patients who had been treated with anlotinib hydrochloride capsules in the past;
- Symptomatic brain metastases (patients with stable symptoms and completed treatment 21 days before enrollment can be enrolled, but no cerebral hemorrhage symptoms should be confirmed by brain MRI, CT or venography evaluation);
- Patients with hypertension who could not be well controlled by single antihypertensive drug treatment (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg); Or use two or more antihypertensive drugs to control blood pressure
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 |
|---|---|---|
| Anlotinib HydrochlorideAnlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once daily, 2 weeks on/1 week off. | Drug | Experimental: anlotinib+mXELIRI |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Through study completion, up to 24 months
The main side effects of drugs are the main reasons for limiting the increase of the dose of chemotherapy drugs, which are dose limiting toxicity of chemotherapy drugs
Phase II clinical recommended dose (RP2D)
Time frame: each 42 days up to intolerance the toxicity or PD
When the minimum number of patients is included in the dose increasing phase, the recommended dose of phase 2 can be determined accurately and quickly
Objective response rate
Time frame: Through study completion, up to 24 months
Objective response rate is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
5 secondary outcomes
Progression free survival
Time frame: From date of enrollment until the date of first documented progression, assessed up to 24 months
Overall survival
Time frame: From date of enrollment until death, assessed up to 24 months
Disease control rate
Time frame: Through study completion, up to 24 months
Duration of remission
Time frame: Through study completion, up to 24 months
Score of quality of Life
Time frame: From date of enrollment until death, assessed up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- 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.
Haibo Zhang, Professor principal investigator
Guangdong Provincial Hospital of Traditional Chinese Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anlotinib Hydrochloride in people with Advanced Colorectal Cancer, run by Guangzhou University of Traditional Chinese Medicine 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 7 inclusion and 26 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 5 Sep 2021. 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 combined 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.
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 Haibo Zhang, Professor (86 20 81887233 ext. 34830, doctorllr@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: Through study completion, up to 24 months). 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 5 Sep 2021.