Status:
UNKNOWN
Phase II Trial of Fruquintinib With Sintilimab in Treating Selected Refractory Metastatic Colorectal Cancer Patients
Lead Sponsor:
Aiping Zhou
Conditions:
Colorectal Cancer
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
This is a prospective, Single arm Phase II trial. Patients were eligible to participate when they had histological or cytological confirmed metastatic colorectal adenocarcinoma Non-MSI(microsatellite ...
Eligibility Criteria
Inclusion
- Fully understand the study and signed the Informed Consent Form (ICF) out of their own will;
- Histologically or cytologically diagnosed with metastasis colorectal adenocarcinoma CRC (Phase IV)
- MSS or MSI-low, MSI was assessed per local guidelines (immunohistochemistry and/or polymerase chain reaction \[PCR\]) prior to screening. Tumor samples with instability in 0 or 1 marker were identified as microsatellite-stable and MSI-low, respectively.
- TMB≥5 mutations/Mb, TMB was performed on plasma samples by NGS.
- Subjects who failed at least second line standard chemotherapies including Fluorouracil, Oxaliplatin, Irinotecan and VEGF inhibitors(e.g., bevacizumab). Pre-treatment with anti-EGFR(e.g., cetuximab) were mandatory if RAS wild and left side. Failed therapies are defined as the occurance of PD or intolerable toxicities during the treatment or within 3 months after the last dose.
- Subject must not receive any systematically anti-tumor therapies during the last 4 weeks, and never receive any vascular endothelial growth factor (VEGFR) inhibitor or Immune checkpoint blockade.
- 18-75 years of age (inclusive)
- Body weight≥40Kg
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Patients capable of taking oral medication
- Patients with evaluable or measurable lesions as per RECIST version 1.1
- Expected survival \>12 weeks
Exclusion
- with MSI-H colorectal adenocarcinoma as defined per local assessment using standard of care testing
- Previous treatment with Fruquintinib or immune checkpoint inhibitors
- Absolute neutrophil count (ANC)\<1.5×109/L, or blood platelet count (PLT)\<100×109/L, or hemoglobin\<90g/L; blood transfusion within 1 week before enrollment for the purpose of enrollment is not allowed;
- Serum total bilirubin\>1.5×Upper Limit of Normal (ULN);Alanine transaminase(ALT) and/or Aspartate transferase (AST)\>2.5×ULN (subject to the normal value at each site); or ALT and/or AST \> 5×ULN for patients with liver metastases;
- Creatinineclearancerate\< 50mL/min;
- Uncontrolled hypertension by monotherapy, i.e. systolic blood pressure \>140mmHg or diastolic blood pressure \>90mmHg after monotherapy treatment.
- Clinical significant electrolyte abnormality;
- Results of urine protein detection with 2+ or above, or urinary protein quantity ≥1.0g/24h;
- Unrecovered toxicity fromprevious anticancer therapies(NCI CTC AE\>Grade 1, except for alopecia and ≤Grade 2 neurotoxicity caused by Oxaliplatin), not fully recovered from previous surgeries; or the time from the last anticancer therapy or surgery is less than 4 weeks;
- Central Nervous System (CNS) metastatic disease or prior cerebral metastasis;
- Subjects with presence of clinically detectable second primary malignant tumors at enrollment, or other malignant tumors within the last 5 years (excluding adequately treated skin basal cell carcinoma or carcinoma in situ of cervix).
- Clinically uncontrolled active infection, such as acute pneumonia, active hepatitis B or hepatitis C(previous medical history of hepatitis B virus infection regardless of drug control, HBV DNA≥104×copynumberor ≥2000IU/mL);
- Difficulty in swallowing or known drug malabsorption;
- Duodenal ulcer, ulcerative colitis, intestinal obstruction, other gastrointestinal diseases or other conditions that may lead to gastrointestinal bleeding or perforation according to the investigator's judgment; or with a history of intestinal perforation or intestinal fistula, which were not fully recovered after surgery;
- History of artery thrombosis or deep venous thrombosis within 6 months before enrollment, or have evidence or a history of bleeding tendency within 2 months before the enrollment, regardless of severity;
- Occurrence of stroke or transient ischemic attack within 12 months before the enrollment;
- Activated Partial Thromboplastin Time (APTT) and/or prothrombin time (PT) \> 1.5×ULN (subject to the normal range at each site);
- Skin wounds, surgical site, trauma site, severe mucosal ulcers or fracture not completely healed;
- Acute myocardial infarction, severe/unstable angina or received coronary artery bypass surgery within 6 months prior to enrollment; or patients with cardiac insufficiency of NYHA Grade 2 or above;
- Pregnant or lactating women Or female subjects with childbearing potentials with positive pregnancy test result before the first time of study drug treatment;
- Any clinical or laboratory abnormalities or compliance concerns unfit to participate in this clinical trial according to the investigator's judgment;
- Serious psychological or psychiatric disorders;
- Contraindications of immune checkpoint inhibitors
- Participated in any other drug clinical trial during the last 4 weeks.
Key Trial Info
Start Date :
September 1 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 30 2022
Estimated Enrollment :
70 Patients enrolled
Trial Details
Trial ID
NCT04695470
Start Date
September 1 2020
End Date
June 30 2022
Last Update
January 7 2021
Active Locations (1)
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1
Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China, 100021