Cadonilimab Combined With Fruquintinib and SBRT as Athird-line and Posterior Line Treatment in Patients With MSS CRC

Huazhong University of Science and Technology

Status and phase

Enrolling

Phase 2

Conditions

Colorectal Cancer

Treatments

Radiation: SBRT

Drug: Cadonilimab

Drug: Fruquintinib

Study type

Interventional

Funder types

Other

Identifiers

NCT06168786

CRC-II-001

Details and patient eligibility

About

A Phase II Study to Assess the Efficacy and Safety of Cadonilimab Combined With Fruquintinib and SBRT as A third-line and Posterior Line Treatment in Patients With MSS Colorectal Cancer

Enrollment

40 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Provision of written Informed Consent Form (ICF) prior to any study specific procedures
Age ≥ 18 years, ≤75 years
Histologically or cytologically confirmed advanced Stage IV primary colorectal cancer
MSI status: MSS
At least two or more standard systemic therapies prior treatment (based on Fu, oxaliplatin, irinotecan, bevacizumab and cetuximab) of cytotoxic chemotherapy, treatment failure or intolerable toxicities
ECOG 0-1
Patients must have measurable lesions
Expected overall survival ≥12 weeks
AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)，Serum bilirubin ≤ 1.5 x ULN，creatinine<ULN
Prothrombin time (PT), international standard ratio (INR) ≤1.5 × ULN
Patients are allowed to have received radiotherapy, but the time from entering the group must be more than 4 weeks, and the currently selected radiotherapy lesions and evaluable lesions must be lesions that have not received radiotherapy
Fertile male or female patients voluntarily used an effective contraceptive method during the study period and within 6 months of the last study medication

Exclusion criteria

Patients have received anti-PD-1 / PD-L1 or anti-CTLA-4 immunotherapy or other immunoexperimental drugs
Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granuloma), etc
Symptomatic interstitial lung disease or active infection/non-infectious pneumonia
Risk factors of intestinal perforation: active diverticulitis, abdominal abscess, gastrointestinal obstruction, abdominal cancer or other known risk factors of intestinal perforation
If the patients underwent surgery, they should wait for the wound to heal completely before being considered for enrollment
History of other malignant tumors（(except for the cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, and breast carcinoma in situ）
Patients who are preparing for or have previously received an organ or allogeneic bone marrow transplant
Moderate or severe ascites with clinical symptoms required therapeutic puncture, drainage or Child-Pugh score >2 (except those who only show a small amount of ascites on imaging without clinical symptoms); Uncontrolled or moderate or higher pleural effusion or pericardial effusion
History of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within 6 months before the start of treatment
Abdominal fistula, gastrointestinal perforation, or abdominal abscess developed within 6 months before the start of study treatment
Known hereditary or acquired bleeding (e.g. coagulation dysfunction) or thrombotic tendencies, e.g. in hemophiliacs; Currently or recently (within 10 days prior to the start of study therapy) used full dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (allowing prophylactic use of low-dose aspirin, low molecular weight heparin)
Aspirin (> 325 mg / day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel (≥ 75 mg) and cilostazol are currently used or have been used recently (within 10 days before the start of study treatment)
Thrombosis or embolism events such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction) and pulmonary embolism occurred within 6 months before the start of the study
Patient with an active infection, heart failure, heart attack, unstable angina pectoris, or unstable arrhythmia within the last 6 months
Physical examination or clinical trial findings that the investigator believes may interfere with the results or put the patient at increased risk for treatment complications, or other uncontrollable diseases
The researchers believe that the patient has a lesion and needs emergency palliative radiotherapy / emergency surgery (spinal cord compression, brain hernia, pathological fracture)
Lactating or pregnant women
History of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation
Patients with mental illness, substance abuse, or social problems that affect compliance will not be enrolled after researcher's review
Known active infection and active tuberculosis infection were not included in the group; However, patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection can be included in the group if their condition is stable after antiviral treatment
Patients who received live vaccine within 30 days prior to enrollment
Have clinical symptoms or diseases of the heart that are not well controlled
Systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg regardless of any antihypertensive drugs； or a history of hypertensive crisis or hypertensive encephalopathy
Major vascular disease (such as aortic aneurysms requiring surgical repair or recent peripheral arterial thrombosis) developed within 6 months
Severe, unhealed or open wounds and active ulcers or untreated fractures
Received major surgery within 4 weeks prior to the start of study treatment (except for diagnosis) or expected to require major surgery during the study period
Inability to swallow tablets, malabsorption syndrome or any condition affecting gastrointestinal absorption
Had a history of intestinal obstruction and/or had clinical signs or symptoms of gastrointestinal obstruction within 6 months prior to initiation of study therapy, including incomplete obstruction related to pre-existing disease or requiring routine parenteral hydration, parenteral nutrition, or tube feeding
Patients with signs/symptoms of incomplete obstruction/obstructive syndrome/ileus at initial diagnosis may be admitted to the study if they have received definitive (surgical) treatment to resolve symptoms
There is evidence of abdominal gas accumulation that cannot be explained by puncture or recent surgical procedures
Metastatic disease involving a major airway or blood vessel or a large mediastinal tumor mass located in the center (<30 mm from the crest)
Patients with a history of hepatic encephalopathy
For those who currently have interstitial pneumonia or interstitial lung disease, or who have a history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, Or other subjects with pulmonary fibrosis, institutionalized pneumonia, pneumoconiosis, drug-related pneumonia, idiopathic pneumonia that may interfere with the judgment and management of immune-related pulmonary toxicity, or with evidence of active pneumonia or severe impairment of lung function visible on chest CT during the screening period, radiation pneumonia is allowed in the radiation field; Active tuberculosis
Presence of active autoimmune disease or history of autoimmune disease with possible recurrence; Participants with non-systemic skin diseases such as vitiligo, psoriasis, and alopecia, controlled type 1 diabetes treated with insulin, or asthma in complete remission in childhood, were enrolled without any intervention as adults; Patients with asthma who require medical intervention with bronchodilators are not included
Use of immunosuppressants or systemic hormone therapy for immunosuppression within 14 days prior to initiation of study therapy
Known history of severe allergy to any monoclonal antibody, anti-angiogenesis targeting drug
Severe infection, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia, in the 4 weeks prior to initiation of study treatment; Therapeutic antibiotics were given orally or intravenously within 2 weeks prior to the start of study therapy
According to the investigator's judgment, the patient has other factors that may affect the study results or lead to the forced termination of the study. There are serious abnormalities in laboratory examination, accompanied by family or social factors, which will affect the safety of the patient