Liposomal Irinotecan Plus Bevacizumab in Irinotecan-refractory Metastatic Colorectal Cancer

NCT06434090 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CSPC-DEY-CRC-K06
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of liposomal irinotecan plus bevacizumab in irinotecan-refractory metastatic colorectal cancer

Conditions

Colorectal Cancer

Keywords

Liposomal irinotecan; bevacizumab

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of liposomal irinotecan

  Defined as the highest dose of DLT in\<33% of subjects .

  1 months

• Objective Response Rate

  Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.

  5 months

Secondary Outcomes (5)

• Dose-Limiting Toxicities (DLT) of liposomal irinotecan

  1 months

• Disease Control Rate

  5 months

• Duration of Response

  5 months

• Progression free Survival

  1 years

• Overall survival

  1 years

Study Arms (1)

Liposomal irinotecan plus bevacizumab

EXPERIMENTAL

Patients received Liposomal irinotecan (a '3+3' design was adopted in the experimental arm, with 3 dose levels of 70mg/m2, 80mg/m2, and 90mg/m2 for dose exploration) every 2 weeks (Q2W). bevacizumab, 5mg/m2, every 2 weeks The two-drug combination therapy was continued every 2 weeks in a cycle until patients developed disease progression or met other criteria for termination of study treatment specified in the protocol.

Drug: Liposomal irinotecan; Drug: Bevacizumab

Interventions

Liposomal irinotecan DRUG

Liposomal irinotecan will be given biweekly at a dose from 70mg/m2 to 90mg/m2.

Liposomal irinotecan plus bevacizumab

Bevacizumab DRUG

bevacizumab will be given biweekly at a dose of 5mg/m2

Also known as: avastin

Liposomal irinotecan plus bevacizumab

Eligibility Criteria

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

You may qualify if:

• Age: ≥18 years old；
• Histopathologically and/or cytologically confirmed unresectable metastatic colorectal adenocarcinoma；
• Previous treatment with irinotecan , and have progression of disease during treatment or within three months thereafter；
• At least one measurable lesion (according to RECIST v1.1)；
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1；
• The expected survival time ≥3 months；
• Adequate bone marrow function : no blood transfusion and/or use of increasing leukocyte drugs (excluding oral medication) within 14 days prior to enrollment Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥100×109/L Hemoglobin (Hgb) ≥90 g/L；
• Adequate hepatic function as evidenced by:
• Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, ≤5 × ULN if liver metastases are present.
• Serum albumin ≥30 g/L； (9Adequate renal function as evidenced by: serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min. proteinuria\<2+（those with proteinuria ≥2+ at baseline had to demonstrate ≤1 g protein per 24 hours）； (10)Coagulation function: International normalised ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5 × ULN； (11)Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening；

You may not qualify if:

• Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc；
• Patients with the primary lesion located in the left colon and RAS/BRAF wild-type who did not use cetuximab on the first-line；
• Patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR)；
• Massive pleural effusion or ascites requiring intervention；
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment；
• Active HIV infection；
• Combined with uncontrollable systemic diseases within 6 months before the first administration；
• Presence of severe gastrointestinal disease；
• History of major surgery (such as laparotomy, thoracotomy or intestinal resection) within 28 days before the first administration,or plan to undergo major surgery during the study period；
• Presence of interstitial pneumonia or pulmonary fibrosis；
• History of allergy or hypersensitivity to drug or any of their excipients；
• History of pulmonary hemorrhage/hemoptysis ≥Grade 2 (defined as bright red blood of at least 2.5mL) within one month before the first administration；
• Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before the first administration；
• Combined symptomatic brain metastasis, meningeal metastasis, spinal cord tumor invasion, and spinal cord compression syndrome；
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1 within 14 days before the first administration；

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

irinotecan sucrosofate; Bevacizumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Yanhong Deng, PhD

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanhong Deng, PhD

CONTACT

020-38379762; dengyanh@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Medical Oncology, Clinical Professor

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: May 30, 2024
• Study Start: June 5, 2024
• Primary Completion: June 5, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)