Status:
UNKNOWN
Tyrosine Kinase Inhibitor (TKI) + Anti-PD-1 Antibody in TKI-responded Microsatellite Stability/Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Adenocarcinoma.
Lead Sponsor:
China Medical University, China
Conditions:
MSS
pMMR
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of fruquintinib or regorafenib in combination with anti-PD-1 antibody in TKI (fruquintinib or regorafenib)-responded MSS/pMMR metastati...
Detailed Description
At present, the later-line treatment of metastatic colorectal cancer (mCRC) can bring benefits to subjects. However, the overall efficacy of treatment is still low. The programmed cell death protein 1...
Eligibility Criteria
Inclusion
- Subjects who voluntarily participated in the study, signed the written informed consent form, and could comply with the protocol of study.
- Male or female of age 18-75 years.
- Subjects with colorectal adenocarcinoma who were histopathologically confirmed, and with locally advanced (unresectable) or mCRC.
- Subjects who underwent standard antitumor therapies (fluorouracil, oxaliplatin, irinotecan were used, with or without administration of bevacizumab and/or cetuximab).
- Patients with MSS/pMMR mCRC (immunohistochemistry, polymerase chain reaction or next-generation sequencing can be used).
- All adverse reactions associated with drug use or surgery were reduced to grade 0-1 (according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) or to a level required by the protocol criteria.
- The presence of at least one measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI).
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
- Subjects with life expectancy ≥ 12 weeks.
- Adequate important organs functions: bone marrow function (neutrophil count ≥ 1.5×10\^9/L; platelet ≥ 80×10\^9/L; hemoglobin ≥ 90 g/L), liver function (serum albumin ≥ 28 g/L; total bilirubin ≤ 1.5×upper limit of normal (ULN); alanine aminotransferase and aspartate aminotransferase ≤ 3×ULN, or ≤ 5×ULN if liver metastases are present), renal function (serum creatinine ≤ 1.5×ULN or creatinine clearance (CrCl) ≥ 40 mL/min, using the Cockcroft-Gault formula; urine protein \< 2+; 24h urinary protein content \< 1.0 g/24h if urinary protein ≥ 2+ ), coagulation function (international normalized ratio or activated partial thromboplastin time ≤ 2×ULN), thyroid function (thyrotropin ≤ 1×ULN).
Exclusion
- Known microsatellite instability high (MSI-H) mCRC.
- Participation in another study with intervention or drugs within the past 4 weeks.
- Performing surgery and incomplete recovery within the past 4 weeks.
- Subjects with active autoimmune diseases or with related history. Subjects with controlled type I diabetes or hypothyroidism with substitution therapy may be included for further screening.
- Any conditions requiring corticosteroids (\> 10 mg per day of prednisone or equivalent) or immunosuppressive drugs as systemic treatment within the past 1 week.
- Other active malignancy within the past 5 years, except for the cured limited cancer (such as basal cell carcinoma, carcinoma in situ of the prostate or cervix, etc.).
- Subjects with history of hepatic encephalopathy or confirmed metastases to central nervous system.
- Subjects with non-infectious pneumonia under steroid treatment within the past 6 months.
- Suffering from chronic or active infections, fever (≥ 38.5℃) within the past 1 week, or white blood cell count \> 15×10\^9/L), requiring systemic anti-infective treatment at the screening period, except for viral hepatitis.
- Subjects with any other abnormal condition that is inconsistent with the study medication, or may increase the risk of the subject，according to investigators' judgment.
- Congenital or acquired immunodeficiency (such as human immunodeficiency virus).
- Subjects with active hepatitis B virus (HBV) (HBV surface antigen positive and HBV-DNA \> 2000 IU/ml) or hepatitis C virus (HCV) (HCV antibody and HCV-RNA positive).
- Subject who received a live attenuated vaccine within the past 4 weeks, or vaccination is planned during anti-PD-1 antibody treatment or within 5 months after the last treatment.
- More than mild pericardial effusion, massive pleural or/and peritoneal effusions need puncture and drainage at the screening period.
- Subjects with symptomatic heart and cerebrovascular diseases: heart failure (New York Heart Association class III or IV, left ventricular ejection fraction \< 50%), uncontrolled hypertension or arrhythmias, serious cardiovascular and cerebrovascular events (acute coronary syndrome, stroke, thromboembolism, etc.) within the past 6 months.
- Known allergy to targeted drugs.
- Women being pregnant, or during lactation, or planning to get pregnant during the trial.
- Subjects with any other conditions judged by investigators would be excluded.
Key Trial Info
Start Date :
July 24 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 31 2022
Estimated Enrollment :
53 Patients enrolled
Trial Details
Trial ID
NCT04483219
Start Date
July 24 2020
End Date
July 31 2022
Last Update
October 5 2021
Active Locations (1)
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1
Cancer Hospital of China Medical University/Liaoning Cancer Hospital &Institute
Shenyang, Liaoning, China, 110042