Phase II Study of Irinotecan Plus Trifluridine/Tipiracil (TAS-102) in Combination With Bevacizumab as a Third-Line or Beyond Therapy for Patients With Metastatic Colorectal Cancer (mCRC)
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
Study Overview
Brief Summary
Currently, the approved third-line treatments for metastatic colorectal cancer (mCRC) include regorafenib, fruquintinib, and trifluridine/tipiracil(TAS-102). In recent years, several phase I/II studies evaluated the combination of TAS-102 and bevacizumab in mCRC patients who were refractory to standard therapies and showed promising antitumor efficacy and manageable toxicity. In this single-center phase II study, the investigators explored the efficacy and safety of irinotecan, TAS-102, plus bevacizumab in a third-line or beyond therapy for patients with mCRC.
Detailed Description
The mCRC patients who are refractory to standard therapies and need a third-line or beyond therapy are eligible. Patients who previously received irinotecan while progressing during maintenance therapy are also eligible.
These patients received an intravenous infusion of irinotecan (150mg/m2 on day 1) plus bevacizumab (5 mg/kg on day 1) and an oral administration of TAS-102(30 mg/m2 given bid on days 1-5), repeated every 14 days.
The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Colorectal adenocarcinoma confirmed histologically or histopathologically.
- •Patients were clinically diagnosed with metastatic colorectal cancer based on computed tomography (CT) scan and magnetic resonance imaging (MRI) according to AJCC 8th edition.
- •Patients must have received standard therapy for mCRC and is refractory or intolerant to those therapies.
- •Age ≥18 and ≤
- •ECOG physical status score is 0 or 1, and no obvious deterioration within 2 weeks prior to use on Day 1 of Cycle
- •Appropriate organ function according to the following laboratory test values:
- •Hemoglobin value ≥90g/L.
- •White blood cell count ≥3.5*109/L.
- •Absolute neutrophil count ≥1.5*109/L.
- •Platelet count ≥100*109/L.
- •Serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance ≥60ml/min.
- •Total serum bilirubin ≤1.5* upper normal limit (ULN).
- •Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5* upper limit of normal value (ULN).
- •Signed the informed consent.
Exclusion Criteria
- •The pathological types were squamous carcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, and other histological types except adenocarcinoma.
- •Patients who had shown hypersensitivity to Irinotecan and Trifluridine/tipiracil (TAS-102) or any other component of them. Patients who previously received irinotecan while disease progressed. However, patients who previously received irinotecan while progressing during maintenance therapy are eligible.
- •Known hypersensitivity to Bevacizumab or hypersensitivity to any other component of Bevacizumab.
- •Patients unable to swallow or lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- •Patients had recurrent episodes of bleeding (risk of gastrointestinal bleeding) or received transfusions in the previous 2 weeks.
- •Major surgery in the previous 4 weeks. (Biopsy is excluded)
- •Previous or concurrent cancer diagnosed within 5 years prior to study inclusion, except for curatively treated in situ cervical cancer, non-melanoma skin cancer, basal cell carcinoma, benign prostate cancer, ductal carcinoma in situ, well-differentiated thyroid cancers and superficial bladder tumors: staged Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor with lamina propria invasion). Carcinomas that can be cured by adequate treatment are also excluded.
- •History of abdominal fistula, gastro-intestinal perforation, intestinal obstruction, chronic diarrhea or inflammatory bowel disease including Crohns disease and ulcerative colitis within 6 months prior to the first study treatment.
- •Patients with severe cardiac dysfunction, such as LVEF< 50%, CHF≥ grade 2, severe/unstable angina, history of stroke or transient ischemic attack or myocardial infarction in the previous 6 months.
- •Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic pressure >100 mmHg despite treatment) and uncontrolled diabetes (fasting plasma glucose > 8.9 mmol/l).
- •Patients with a history of ventricular tachycardia, torsades de pointes, prolonged QTc, complete left bundle branch block or third-degree atrioventricular conduction block..
- •Patients with active hepatitis B, hepatitis C, syphilis or human immunodeficiency virus infection.
- •Arterial or venous thrombotic or embolic events such as deep vein thrombosis, and pulmonary embolism within 6 months of starting study treatment (catheter-related thrombosis is excluded).
- •Patients with active pulmonary tuberculosis were taking anti-tuberculosis treatment or have taken anti-tuberculosis treatment within 12 months of starting study treatment.
- •Patients with severe primary respiratory diseases, interstitial lung disease, or history of pneumonitis.
- •Patients with current active infections requiring anti-infection treatment within 2 weeks of starting study treatment.
- •Patients with a history of psychiatric drug abuse or a history of drug abuse.
- •Pregnant or lactating women.
- •Patients of childbearing potential are unwilling to practice contraception.
Arms & Interventions
Irinotecan, TAS-102 plus Bevacizumab arm
Patients received an intravenous infusion of irinotecan (150mg/m2 on day 1) plus bevacizumab (5 mg/kg on day 1) and an oral administration of TAS-102(30 mg/m2 given bid on days 1-5), repeated every 14 days.
Intervention: Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 36 months
The proportion of patients with a confirmed complete response or partial response using RECIST 1.1
Secondary Outcomes
- Progression-Free Survival (PFS)(36 months)
- Overall Survival (OS)(36 months)
- Safety and tolerability by incidence, severity and outcome of adverse events(36 months)