Irinotecan, TAS-102 Plus Bevacizumab as a Second-Line Therapy in mCRC Patients

NCT06202001 | Recruiting Phase 1

• 1 other identifier: NCC3945
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

In mCRC, response to second-line chemotherapy is limited, and few treatment options are available. It is urgent to design an optimal second-line treatment regimen to improve the response rate and prolong the survival of patients with mCRC. Several studies preliminarily demonstrated that irinotecan, TAS-102 plus bevacizumab regimen could bring promising efficacy with a tolerable safety profile for patients with mCRC as a second-line treatment. This phase I/II study was aimed to determine the recommended phase II dose (RP2D) of the combination of TAS-102, irinotecan, and bevacizumab for future clinical trials in patients with mCRC refractory to both fluoropyrimidine and oxaliplatin and to evaluate its safety and preliminary efficacy.

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

This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days.

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

Interventions

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

This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), 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 have received oxaliplatin-based first-line chemotherapy with or without targeted therapy, immunotherapy or radiotherapy.
• 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 3 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)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

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

Central Study Contacts

Yongkun Sun

CONTACT

+8613141276041; hsunyk@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2024
• First Posted: January 11, 2024
• Study Start: October 1, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 2, 2024

Record last verified: 2024-04

Locations

CN (1)