Irinotecan, TAS-102 Plus Bevacizumab as a Third-Line or Beyond Therapy in mCRC Patients

NCT06403709 | Active Not Recruiting Phase 2

• 1 other identifier: SH-2023005
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients with a confirmed complete response or partial response using RECIST 1.1

  36 months

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  36 months

• Overall Survival (OS)

  36 months

• Safety and tolerability by incidence, severity and outcome of adverse events

  36 months

Study Arms (1)

Irinotecan, TAS-102 plus Bevacizumab arm

EXPERIMENTAL

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.

Drug: Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab

Interventions

Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab DRUG

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.

Also known as: Irinotecan+TAS-102+Bevacizumab

Irinotecan, TAS-102 plus Bevacizumab arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤70.
• ECOG physical status score is 0 or 1, and no obvious deterioration within 2 weeks prior to use on Day 1 of Cycle 1.
• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Beijing Chaoyang Sanhuan Cancer Hospital

Beijing, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Trifluridine; tipiracil; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Yongkun Sun

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: May 8, 2024
• Study Start: August 1, 2022
• Primary Completion: August 1, 2024
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)