Trial Title:
Neoadjuvant Fruquintinib Plus Tislelizumab Combined With mCapeOX Versus CapeOX for Mid-high pMMR/MSS Locally Advanced Rectal Cancer
NCT ID:
NCT06443671
Condition:
Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Tislelizumab
Conditions: Keywords:
local advanced rectal cancer
neoadjuvant chemotherapy
pMMR/MSS
Furoquinib and Tislelizumab
CapeOX
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CapeOX
Description:
Receiving CapeOX treatment for up to four cycles before surgery:
Capecitabine: 1000mg/m2, BID, PO, D1-14, Q3W; Oxaliplatin: 130 mg/m2, intravenous drip
for 0-2 hours, D1, Q3W.
Arm group label:
CapeOX group
Intervention type:
Drug
Intervention name:
Fruquintinib and Tislelizumab combined with mCapeOX
Description:
Receiving Fruquintinib plus Tislelizumab combined with mCapeOX treatment for up to four
cycles before surgery:
Fruquintinib: 3mg/d, QD, PO, Use for 2 weeks, stop for 1 week, Q3W; Tislelizumab: 200mg,
D1, Intravenous infusion, Q3W; Capecitabine: 825mg/m2, BID, PO, D1-14, Q3W; Oxaliplatin:
100 mg/m2, intravenous drip for 0-2 hours, D1, Q3W.
Arm group label:
Fruquintinib and Tislelizumab combined with mCapeOX
Summary:
The goal of this clinical trial is to learn if neoadjuvant Fruquintinib and Tislelizumab
combined with mCapeOX works to treat mid-high pMMR/MSS locally advanced rectal cancer
patients compared with CapeOX. It will also learn about the safety of neoadjuvant
Fruquintinib and Tislelizumab combined with mCapeOX. The main questions it aims to answer
are:
- Does neoadjuvant Fruquintinib and Tislelizumab combined with mCapeOX improve the pCR
rate of mid-high pMMR/MSS locally advanced rectal cancer patients?
- What medical problems do participants have when receiving neoadjuvant Fruquintinib
and Tislelizumab combined with mCapeOX? Researchers will compare Fruquintinib and
Tislelizumab combined with mCapeOX to CapeOX to see if neoadjuvant Fruquintinib and
Tislelizumab combined with mCapeOX works to treat mid-high pMMR/MSS locally advanced
rectal cancer patients.
Participants will:
- Receive Fruquintinib and Tislelizumab combined with mCapeOX or CapeOX before surgery
up to 4 cycles
- Receive radical operations and three years follow-up
- Keep a diary of their postoperative pathology results and survival
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The subjects voluntarily joined this study and signed an informed consent form;
- Age: 18-75 years old (including 18 and 75 years old), regardless of gender;
- Histologically confirmed rectal adenocarcinoma; Immunohistochemistry suggests pMMR,
or PCR suggests MSS type patients;
- The tumor location meets the following criteria:
1. Colonoscopy or digital examination shows that the distance from the lower edge
of the tumor to the anus is 6-15cm or more than 4cm from the ARJ;
2. MRI/CT determines that the lower edge of the tumor or the lower edge of the
invading part is not higher than the sacral promontory pubic line;
- Preoperative staging meets the following conditions:
1. Preoperative staging of tumor infiltration breaking through the intestinal
muscle layer (T3) or above or accompanied by periintestinal lymph node
metastasis;
2. Non invasion of the intrinsic fascia of the rectum (MRF -);
3. No swelling observed in lateral lymph nodes (short diameter not exceeding 7mm)
4. There is no clear evidence of distant metastasis, and R0 resection is expected
to be feasible after treatment; *Baseline partial phase method: Rectal T2/DWI
MR or Abdominal Pelvic CT or PET/CT or PET/MRI;
- Have not received any anti-tumor treatment for rectal cancer in the past, including
surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc;
- ECOG score: 0-1 points;
- Able to swallow tablets and capsules normally;
- The plan is to complete the entire process of neoadjuvant therapy and undergo
surgical resection;
- The main organs and bone marrow function are basically normal (no blood components
or cell growth factors were used within 14 days before enrollment):
1. Blood routine: Neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥
90g/L;
2. International standardized ratio (INR) ≤ 1.5 x Upper limit of normal value
(ULN), and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
3. Liver function: Total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 2.5 x ULN；
4. Renal function: serum creatinine ≤ 1.5 x ULN, and creatinine clearance rate
(CCr) ≥ 50mL/min;
- Women of childbearing age must undergo a serum pregnancy test within 14 days before
treatment, and the result is negative; Qualified patients with fertility (male and
female) must agree to use reliable contraceptive methods (hormone or barrier methods
or abstinence, etc.) with their partners during the trial period and at least 6
months after the last medication.
Exclusion Criteria:
- Have a history of allergies to any anti-angiogenic targeted drugs, any components of
monoclonal antibodies, capecitabine, oxaliplatin, or other platinum-based drugs in
the past;
- Preoperative evidence suggests distant metastasis (including lymph node metastasis
in the iliac foramen area) Metastasis of aortic lymph nodes and retroperitoneal
lymph nodes above the root level of IMA; In addition to clear liver lung metastasis,
liver lung nodules with unknown properties should also be excluded;
- Symptoms of incomplete or complete intestinal obstruction; Or preoperative
colonoscopy may indicate narrowing of the intestinal lumen circumference; Or if the
tumor is too large, colonoscopy cannot pass through the tumor;
- Those who are currently using immunosuppressive agents, systemic or absorbable local
hormone therapy to achieve immunosuppressive effects (dosage>10mg/day
prednisone or other therapeutic hormones), and continue to use them within 2 weeks
prior to enrollment;
- Receive attenuated live vaccines within 4 weeks prior to the first use of the study
drug;
- Any active autoimmune disease or history of autoimmune disease (such as but not
limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,
hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism,
hypothyroidism; subjects with vitiligo or complete remission of childhood asthma in
adulthood without any intervention can be included; subjects with asthma requiring
medical intervention with bronchodilators cannot be included);
- Other malignant tumors in the past 5 years (excluding skin basal cell or squamous
cell carcinoma, cervical carcinoma in situ, breast cancer, thyroid papillary
carcinoma and small kidney carcinoma that are clinically cured after proper
treatment (OS>5 years));
- Congenital or acquired immune deficiency (such as HIV infected persons), or active
hepatitis (hepatitis B: HBsAg positive and HBV DNA ≥ 104 copies/ml; hepatitis C: HCV
antibody positive and HCV RNA>1 × 103 copies/ml);
- Have uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA
grade 2 or above heart failure; (2) Unstable angina pectoris; (3) Have experienced
myocardial infarction within one year; (4) Clinically significant supraventricular
or ventricular arrhythmias require treatment or intervention;
- Suffering from hypertension and unable to achieve good control through
antihypertensive drug treatment (systolic blood pressure ≥ 150 mmHg or diastolic
blood pressure ≥ 100 mmHg);
- Active or uncontrolled severe infections (≥ CTCAE level 2 infection);
- Urinary routine indicates that urine protein is ≥ 2+, and the 24-hour urine protein
content is>1.0g;
- Known genetic or acquired bleeding and thrombotic tendencies (such as hemophilia,
coagulation dysfunction, thrombocytopenia, splenic hyperfunction, etc.) or
undergoing thrombolytic or anticoagulant therapy;
- The patient currently has digestive tract diseases such as active gastric and
duodenal ulcers, ulcerative colitis, or active bleeding from unresectable tumors, or
other conditions determined by the researcher that may cause gastrointestinal
bleeding or perforation;
- Patients with significant evidence of bleeding tendency or medical history within
the 3 months prior to enrollment (bleeding>30 mL within 3 months, vomiting
blood, black stool, and rectal bleeding), hemoptysis (fresh blood>5 mL within
4 weeks), or thromboembolic events (including stroke events and/or transient
ischemic attacks) within 12 months;
- Pregnant (positive pregnancy test before medication) or breastfeeding women;
- According to the judgment of the researchers, the subjects may have other situations
that may affect the results of the study or cause the study to be forced to stop
midway, such as drug abuse, serious illnesses (including mental illnesses such as
seizures), and other medical, psychological, or social conditions that may endanger
patient safety and compliance.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking University Cancer Hospital & Institute
Address:
City:
Beijing
Zip:
100142
Country:
China
Contact:
Last name:
Xiao Kang Lei, M.D.
Phone:
108-819-6086
Email:
lxkpku@163.com
Start date:
June 1, 2024
Completion date:
June 1, 2028
Lead sponsor:
Agency:
Peking University Cancer Hospital & Institute
Agency class:
Other
Source:
Peking University Cancer Hospital & Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06443671
