PD-1 Inhibitor Combined With Bevacizumab and FOLFIRI Regimen in the Second-line Treatment of Advanced Colorectal Cancer

Phase II Clinical Study on Efficacy and Safety of PD-1 Inhibitor Combined With Bevacizumab and FOLFIRI Regimen in the Second-line Treatment of Unresectable Recurrent or Metastatic MSI-H Colorectal Cancer

MSI-H is a biomarker for solid tumors benefiting from immunotherapy. Recent clinical studies have confirmed that PD-1 inhibitors have a good effect on MSI-H advanced colorectal cancer for first- or second-line treatment. The overall effective rate is 30% to 40%. However, about 30% of patients are resistant to PD-1 inhibitors. Whether PD-1 inhibitors and existing chemotherapeutics and anti-vascular drugs have synergistic effects is worth studying. This study is a phase II prospective clinical study of PD-1 inhibitor combined with bevacizumab and FOLFIRI regimen in the second-line treatment of unresectable recurrent or metastatic MSI-H colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: MSI-H Advanced Colorectal Cancer
• Intervention / Treatment: Drug: Pembrolizumab (PD-1 Inhibitor) Combined With Bevacizumab and FOLFIRI Regimen

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongli Li, Dr.; Phone Number: 1051 86-22-23340123; Email: hongli@126.com
• Study Contact Backup: Name: Tao Ning, Dr.; Phone Number: 1051 86-22-23340123; Email: ningtao37@163.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital
      • Contact: Dongyan Cheng, Dr
      • Principal Investigator: Hongli Li, Dr.
      • Principal Investigator: Yi Ba, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Recurrent or metastatic unresectable colorectal adenocarcinoma confirmed by histology and/or cytology; 2. First-line oxaliplatin-containing chemotherapy has disease progression during chemotherapy or within 6 months after chemotherapy; 3. MSI-H patients confirmed by pathology, MSH2(-) or MSH6(-), for MLH1(-) or PMS2(-) patients need PCR confirmation; 4. According to the RECIST 1.1 standard, there is at least one measurable lesion； 5. Sufficient bone marrow function, liver and kidney function； 6. age greater than 18 years old， less than or equal to 75 years old； 7. ECOG score 0 or 1; expected survival time greater than 3 months; signed informed consent.

Exclusion Criteria:

• 1. For patients who have been treated with PD-1 in the first-line treatment, bevacizumab is allowed in the first-line treatment; 2. Other malignant tumors have been diagnosed within 5 years before the first use of the study drug, except for effectively treated skin basal cell carcinoma, skin squamous cell carcinoma, and/or effectively resected in situ cervical cancer and/or breast cancer; 3. Suffer from any active autoimmune disease or have a history of autoimmune disease; 4. Are suffering from an active infection that requires systemic treatment; 5. The HIV test result is positive; 6. Known to be allergic to certain components of the research drug or similar drugs; 7. Use clinical investigational drugs within 4 weeks before the start of study administration; 8. Major surgery has been performed within 4 weeks before the start of the study administration and has not fully recovered; 9. The patient has a bleeding disorder, and the investigator judges that there is a risk of hemorrhage; 10. Uncontrolled cardiac clinical symptoms or disease heart function, such as severe arrhythmia, uncontrollable hypertension; 11. According to the judgment of the investigator, the subject has other factors that may cause him to be forced to suspend the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experiment Group	Drug: Pembrolizumab (PD-1 Inhibitor) Combined With Bevacizumab and FOLFIRI Regimen; MSI-H colorectal cancer, recurrence and metastasis within 1 year after surgery, or failure of first-line oxaliplatin and fluorouracil chemotherapy for advanced colorectal cancer, PD-1 inhibitors combined with bevacizumab and FOLFIRI regimen; Other Names: Leucovorin; Bevacizumab; Irinotecan; Fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	Up to one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	up to 3 years
Progression-free survival	up to 2 years
Disease Control Rate	Up to 2 years
Adverse Events	up to one year

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Pembrolizumab; Leucovorin; Irinotecan; Immune Checkpoint Inhibitors
• Other Study ID Numbers: TJMUCH-GI-CRC02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No