Trial 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
NCT ID:
NCT06234007
Condition:
Locally Advanced Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Capecitabine
Oxaliplatin
Conditions: Keywords:
Neoadjuvant
Fruquintinib
Colorectal cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine
Description:
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;
Arm group label:
SCRT followed by fruquintinib plus adebrelimab and CAPOX
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent and volunteered to participate in the study;
2. Age 18-75 years old (including the cut-off value), male or female;
3. Locally advanced rectal adenocarcinoma confirmed by histopathology;
4. 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
5. The distance between the lower edge of the tumor and the anal edge is ≤10cm;
6. Able to swallow tablets and capsules normally;
7. ECOG PS 0-1
8. Have not received any anti-tumor treatment for rectal cancer, including surgery,
radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
9. Plan to undergo surgery after completion of total neoadjuvant therapy;
10. No surgical contraindications;
11. Normal major organ function, including:
1. 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
2. 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)
3. Coagulation function:
- International Normalized ratio (INR) ≤ 1.5×ULN
- Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
- Prothrombin time (PT) ≤1.5×ULN
4. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF)≥50%
12. 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;
Exclusion Criteria:
1. Previous allergic history to any anti-angiogenesis targeted drug, any component of
monoclonal antibody, capecitabine, oxaliplatin, or other platinum drugs;
2. 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;
3. 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.
4. A history of immunodeficiency, including HIV positive, other acquired or congenital
immunodeficiency diseases, or organ transplantation or allogeneic bone marrow
transplantation;
5. 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%;
6. 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;
7. 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;
8. 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);
9. The patient had a second primary malignancy;
10. Pregnant or lactating women;
11. History of arterial/venous thrombosis events within 6 months, such as
cerebrovascular accident (including transient ischemic attack), deep vein thrombosis
and pulmonary embolism;
12. Persons with a history of psychotropic drug abuse and inability to quit or with
mental disorders;
13. Patients with any constitutional sign or history of bleeding regardless of severity;
14. Patients with high risk of bleeding, such as active bleeding or bleeding tendency;
15. Urine routine test showed urine protein ≥++, and confirmed 24-hour urine protein
quantitation > 1.0 g;
16. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Contact:
Last name:
Tao Zhang, Ph.D
Phone:
13808640033
Email:
taozhangxh@hust.edu.cn
Investigator:
Last name:
Tao Zhang, Ph.D
Email:
Principal Investigator
Investigator:
Last name:
KaiXiong Tao, Ph.D
Email:
Principal Investigator
Investigator:
Last name:
Zhenyu Lin, Ph.D
Email:
Sub-Investigator
Start date:
December 1, 2023
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Collaborator:
Agency:
Renmin Hospital of Wuhan University
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06234007
