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)
Overview
- Phase
- Phase 2
- Intervention
- Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine
- Conditions
- Locally Advanced Rectal Cancer
- Sponsor
- Wuhan Union Hospital, China
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- pathology complete response(pCR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief 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.
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.
Investigators
Tao Zhang
Professor
Wuhan Union Hospital, China
Eligibility Criteria
Inclusion Criteria
- •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
- •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;
Exclusion Criteria
- •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.
- •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;
Arms & Interventions
SCRT followed by fruquintinib plus adebrelimab and CAPOX
Intervention: Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine
Outcomes
Primary Outcomes
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).
Secondary Outcomes
- R0 resection rate(up to 6 months)
- 3-year Event-Free Survival(EFS) rate(up to 36 months)
- Overall Survival(OS)(up to 36 months)
- Adverse events (AEs)(up to 36 months)