Locally Advanced Rectal CancerPhase 2NCT06234007
Short-course Radiotherapy Followed by Fruquintinib Plus Adebrelimab and CAPOX in the Full Course Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Multicenter, Single-arm, Open-label Study
A Phase 2 study testing Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine in people with Locally Advanced Rectal Cancer, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial summary
To investigate the efficacy and safety of short-course radiotherapy sequential fruquintinib in combination with adebrelimab and CAPOX (full course neoadjuvant therapy) in patients with locally advanced rectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2023to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Signed written informed consent and volunteered to participate in the study;
- Age 18-75 years old (including the cut-off value), male or female;
- Locally advanced rectal adenocarcinoma confirmed by histopathology;
- High risk on pelvic MRI [one of the following criteria] :
- Clinical tumor (cT) stage cT4a or cT4b (according to the AJCC, 8th edition)
- Extramural vascular infiltration
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- Clinical lymph node (cN) stage cN2 (according to the AJCC, 8th edition)
- Involvement of the mesenteric fascia
- Enlarged lateral lymph nodes
- The distance between the lower edge of the tumor and the anal edge is ≤10cm;
- Able to swallow tablets and capsules normally;
- ECOG PS 0-1
- Have not received any anti-tumor treatment for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
- Plan to undergo surgery after completion of total neoadjuvant therapy;
- No surgical contraindications;
- Normal major organ function, including:
- Routine blood test (no blood transfusion and blood products within 14 days prior to the first treatment, no correction with G-CSF and other hematopoietic stimulating factors) :
- Neutrophil count ≥ 1.5×109/L
- Platelet count ≥ 100×109/L
- Hemoglobin ≥ 90 g/L
- White blood cell count ≥ 3.0×109/L
- Blood biochemical tests:
- Total bilirubin ≤ 1.5×ULN (Gilbert's syndrome subjects, ≤3×ULN; Tumor liver metastasis, total bilirubin ≤3×ULN)
- ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN (≤5×ULN for patients with liver metastases)
- Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 50 mL/min (Cocheroft-Gault formula, see Annex 2)
- Coagulation function:
- International Normalized ratio (INR) ≤ 1.5×ULN
- Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
- Prothrombin time (PT) ≤1.5×ULN
- Doppler ultrasound assessment: left ventricular ejection fraction (LVEF)≥50%
- Female subjects of childbearing potential were required to have a negative serum pregnancy test within 14 days before starting the trial drug and to have used an effective contraceptive method (e.g., an intrauterine device, contraceptive pill, or condom) during the trial and for at least 6 months after the last dose; Male participants whose partner is a woman of childbearing potential should use effective contraception during the trial and for 6 months after the last dose;
Who cannot join
- Previous allergic history to any anti-angiogenesis targeted drug, any component of monoclonal antibody, capecitabine, oxaliplatin, or other platinum drugs;
- Have received or are receiving any of the following:
- being treated with an immunosuppressive drug, or systemic hormone, for immunosuppression within 2 weeks before the first dose of the study drug (dose\> 10mg/ day prednisone or equivalent); Inhaled or topical steroid use and dosage are allowed in the absence of active autoimmune disease; Prednisone 10mg/ day or equivalent dose of adrenocortical hormone replacement;
- received live attenuated vaccine within 4 weeks before the first dose of study drug;
- major surgery or severe trauma within 4 weeks before the first dose of study drug;
- Have any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy); Patients with psoriasis or complete remission of childhood asthma/allergies without any intervention in adulthood were considered for inclusion, but patients requiring medical intervention with bronchodilators were not included.
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- A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
- The presence of uncontrolled cardiac symptoms or diseases, including but not limited to: (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias without or poorly controlled after clinical intervention; (5) patients with hypertension that is not well controlled with a single antihypertensive drug (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100mmHg), or patients using two or more antihypertensive drugs to control blood pressure; (6) New York Heart Association (NYHA) functional class \> Grade II or left ventricular ejection fraction (LVEF) < 50%;
- Severe infection (CTCAE > 2) occurred within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; Prophylactic antibiotics were excluded if there was active pulmonary inflammation on baseline chest imaging, if there were signs and symptoms of infection within 14 days before the first dose of study drug, or if oral or intravenous antibiotics were required;
- Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
- Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive, and HCV RNA above the detection limit of the analytical method);
- The patient had a second primary malignancy;
- Pregnant or lactating women;
- History of arterial/venous thrombosis events within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism;
- Persons with a history of psychotropic drug abuse and inability to quit or with mental disorders;
- Patients with any constitutional sign or history of bleeding regardless of severity;
- Patients with high risk of bleeding, such as active bleeding or bleeding tendency;
- Urine routine test showed urine protein ≥++, and confirmed 24-hour urine protein quantitation > 1.0 g;
- According to the investigator's judgment, there are other factors that may lead to the forced termination of the study, such as other serious diseases (including mental diseases) requiring combined treatment, alcohol abuse, drug abuse, family or social factors, and factors that may affect the safety or compliance of the subjects.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan
Tao Zhang, Ph.D, 13808640033, taozhangxh@hust.edu.cn
Tao Zhang, Ph.D
About this study
Official title: Short-course Radiotherapy Followed by Fruquintinib Plus Adebrelimab and CAPOX in the Full Course Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Multicenter, Single-arm, Open-label Study (UNION PRECISION-I)
To investigate the efficacy and safety of short-course radiotherapy sequential fruquintinib in combination with adebrelimab and CAPOX (full course neoadjuvant therapy) in patients with locally advanced rectal cancer.
Read the detailed description
This study was a multicenter, single-arm, open-label clinical trial. The study included a screening period (within 21 days after signing the informed consent form to the first treatment), a treatment period (including total neoadjuvant and surgical treatment), and a follow-up period (including safety and survival follow-up).
Total neoadjuvant therapy:
- Short-course radiotherapy followed by 6 cycles of fuquinitinib combined with adbelimumab and CAPOX followed by surgical resection after 1 week of rest;
- A treatment time window of ±3 days was allowed during the study treatment, but within 3 days before each treatment, in addition to the required imaging examinations, participants were required to complete laboratory tests, physical examinations (as needed), ECOG scores and other safety assessments to determine that they could still tolerate the study treatment. The safety of the subjects was continuously assessed during the study.
- Total Mesorectal Excision (TME) is recommended for radical resection of rectal cancer.
- Conditions
- Locally Advanced Rectal Cancer
- Being tested
- Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine
- Keywords
- Neoadjuvant, Fruquintinib, Colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fruquintinib, Adebrelimab, Oxaliplatin, CapecitabineDrug
Safety run-in phase: Fruquintinib 4mg/d, oral, once daily, continuous treatment for 2 weeks, 1 week off, q3w, 6 cycles; If the number of patients experiencing dose-limiting toxicity (DLT) was ≤1, the study would continue at that dose level. If the number of patients with DLTs was >1, the dose of fruquintinib was decreased to 3mg/d, qd po, d1-14, q3w, and the dose expansion phase was continued；Adebrelimab 1200mg, d1, IV infusion, q3W, 6 cycles; Capecitabine 1000 mg/m2, twice a day, po, d1-14, followed by 7 days of rest, q3W, 6 cycles; Oxaliplatin 130 mg/m2, d1, q3W, 6 cycles;
Dose expansion phase: Fruquintinib RP2D, qd po, d1-14, q3w, 6 cycles; Adebrelimab 1200mg, d1, IV infusion, q3W, 6 cycles; Capecitabine 1000 mg/m2, twice a day, po, d1-14, followed by 7 days of rest, q3W, 6 cycles; Oxaliplatin 130 mg/m2, d1, q3W, 6 cycles;
| Study group | Role | What they receive |
|---|---|---|
| SCRT followed by fruquintinib plus adebrelimab and CAPOX | Experimental | Not described Receives: Drug: Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathology complete response(pCR)
The proportion of subjects with no residual viable tumor cells(ypT0N0) in the primary tumor and lymph nodes, also defined as the proportion of subjects with grade 0 in the AJCC Tumor Regression Grading (TRG) scoring system(version 8.0).
Measured: up to 6 months
Secondary outcomes (4)
3-year Event-Free Survival(EFS) rate
The percentage of patients without disease recurrence or progression or death due to any cause after 3-year follow-up
Measured: up to 36 months
Overall Survival(OS)
The time from the date of randomization to the death caused by any cause
Measured: up to 36 months
R0 resection rate
The rate of negative margin microscopically
Measured: up to 6 months
Adverse events (AEs)
Adverse events (AEs) were graded according to the NCI CTCAE version 5·0
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study start1 Dec 2023
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- More trials run by Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Renmin Hospital of Wuhan University
- Responsible party
- Principal investigator, Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Tao Zhang, Ph.D, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyKaiXiong Tao, Ph.D, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06234007
- Sponsor's protocol ID
- HMPL-013-FLAG-C128
- Status last verified
- Mar 2024
- First submitted
- 13 Nov 2023
- Last updated
- 18 Mar 2024
- Results posted
- 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 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-course Radiotherapy Followed by Fruquintinib Plus Adebrelimab and CAPOX in the Full Course Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Multicenter, Single-arm, Open-label Study (UNION PRECISION-I)
- ClinicalTrials.gov ID
- NCT06234007
- Acronym / sponsor ID
- HMPL-013-FLAG-C128
- Conditions
- Locally Advanced Rectal Cancer
- Keywords
- Neoadjuvant, Fruquintinib, Colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Collaborators
- Renmin Hospital of Wuhan University
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 31 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.
To investigate the efficacy and safety of short-course radiotherapy sequential fruquintinib in combination with adebrelimab and CAPOX (full course neoadjuvant therapy) in patients with locally advanced rectal cancer.
Detailed description
This study was a multicenter, single-arm, open-label clinical trial. The study included a screening period (within 21 days after signing the informed consent form to the first treatment), a treatment period (including total neoadjuvant and surgical treatment), and a follow-up period (including safety and survival follow-up).
Total neoadjuvant therapy:
- Short-course radiotherapy followed by 6 cycles of fuquinitinib combined with adbelimumab and CAPOX followed by surgical resection after 1 week of rest;
- A treatment time window of ±3 days was allowed during the study treatment, but within 3 days before each treatment, in addition to the required imaging examinations, participants were required to complete laboratory tests, physical examinations (as needed), ECOG scores and other safety assessments to determine that they could still tolerate the study treatment. The safety of the subjects was continuously assessed during the study.
- Total Mesorectal Excision (TME) is recommended for radical resection of rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SCRT followed by fruquintinib plus adebrelimab and CAPOX | Experimental | Drug: Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Signed written informed consent and volunteered to participate in the study;
- Age 18-75 years old (including the cut-off value), male or female;
- Locally advanced rectal adenocarcinoma confirmed by histopathology;
- High risk on pelvic MRI [one of the following criteria] :
- The distance between the lower edge of the tumor and the anal edge is ≤10cm;
Key exclusion criteria (19 listed)
- Previous allergic history to any anti-angiogenesis targeted drug, any component of monoclonal antibody, capecitabine, oxaliplatin, or other platinum drugs;
- Have received or are receiving any of the following:
- Have any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy); Patients with psoriasis or complete remission of childhood asthma/allergies without any intervention in adulthood were considered for inclusion, but patients requiring medical intervention with bronchodilators were not included.
- A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
- The presence of uncontrolled cardiac symptoms or diseases, including but not limited to: (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias without or poorly controlled after clinical intervention; (5) patients with hypertension that is not well controlled with a single antihypertensive drug (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100mmHg), or patients using two or more antihypertensive drugs to control blood pressure; (6) New York Heart Association (NYHA) functional class \> Grade II or left ventricular ejection fraction (LVEF) < 50%;
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 |
|---|---|---|
| Fruquintinib, Adebrelimab, Oxaliplatin, CapecitabineSafety run-in phase: Fruquintinib 4mg/d, oral, once daily, continuous treatment for 2 weeks, 1 week off, q3w, 6 cycles; If the number of patients experiencing dose-limiting toxicity (DLT) was ≤1, the study would continue at that dose level. If the number of patients with DLTs was >1, the dose of fruquintinib was decreased to 3mg/d, qd po, d1-14, q3w, and the dose expansion phase was continued；Adebrelimab 1200mg, d1, IV infusion, q3W, 6 cycles; Capecitabine 1000 mg/m2, twice a day, po, d1-14, followed by 7 days of rest, q3W, 6 cycles; Oxaliplatin 130 mg/m2, d1, q3W, 6 cycles; Dose expansion phase: Fruquintinib RP2D, qd po, d1-14, q3w, 6 cycles; Adebrelimab 1200mg, d1, IV infusion, q3W, 6 cycles; Capecitabine 1000 mg/m2, twice a day, po, d1-14, followed by 7 days of rest, q3W, 6 cycles; Oxaliplatin 130 mg/m2, d1, q3W, 6 cycles; | Drug | SCRT followed by fruquintinib plus adebrelimab and CAPOX |
Primary outcome
pathology complete response(pCR)
Time frame: up to 6 months
The proportion of subjects with no residual viable tumor cells(ypT0N0) in the primary tumor and lymph nodes, also defined as the proportion of subjects with grade 0 in the AJCC Tumor Regression Grading (TRG) scoring system(version 8.0).
4 secondary outcomes
3-year Event-Free Survival(EFS) rate
Time frame: up to 36 months
Overall Survival(OS)
Time frame: up to 36 months
R0 resection rate
Time frame: up to 6 months
Adverse events (AEs)
Time frame: up to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- 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.
Tao Zhang, Ph.D principal investigator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
KaiXiong Tao, Ph.D principal investigator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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 Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine in people with Locally Advanced Rectal Cancer, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology 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 31 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 18 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact zhenyu Lin, Ph.D (+8615827130393, whxhlzy@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathology complete response(pCR) (time frame: up to 6 months). 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 18 Mar 2024.