Efficacy and Safety of SBRT Followed by Tislelizumab Plus Cetuximab and Irinotecan in Patients With Previously Treated RAS Wild-type Advanced Refractory Colorectal Cancer

Efficacy and Safety of SBRT Followed by Tislelizumab Plus Cetuximab and Irinotecan in Patients With Previously Treated RAS Wild-type Advanced Refractory Colorectal Cancer: a Phase II, Single-arm Study

To evaluate the efficacy and safety of SBRT followed by tislelizumab plus cetuximab and irinotecan in patients with previously treated RAS wild-type advanced refractory colorectal cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Irinotecan Hydrochloride; Drug: cetuximab; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Anticipated): 23
• Phase: Phase 2

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:

• Aged 18-75 years
• Physical Condition Score (ECOG PS) of the Eastern Cancer Cooperative Group (USA) 0 or 1;
• Colorectal cancer diagnosed histologically and/or cytologically has metastases or relapses that are not curable by surgery
• Have received first - and second-line systemic antitumor therapy for mCRC (chemotherapy drugs may include fluorouracil, oxaliplatin, irinotecan, e.g. XELOX, FOLFOX, FOLFIRI, FOLFOXIRI, XELIRI; Can be combined with or without targeted drugs, such as cetuximab, bevacizumab);And disease progression after second-line treatment;
• Evaluation of lung or liver metastases can be evaluated, with stereotactic radiotherapy maneuverability;
• At least one measurable lesion as defined in RECIST version 1.1;
• Fertile patients must be willing to take effective pregnancy avoidance measures during the study period and ≥120 days after the last dose; Female patients with negative urine or serum pregnancy test results within 7 days or less before the first administration of the study drug;
• Have fully understood this study and voluntarily signed informed consent.

• Adequate organ and bone marrow function, meeting the following definitions:

  1. Blood routine (no blood transfusion, no granulocyte colony stimulating factor [G-CSF], no other drug correction within 14 days before treatment);Absolute count of neutrophils (ANC) ≥1.5×109/L;Hemoglobin (HB) ≥9.0 g/dL;Platelet count (PLT) ≥80×109/L;
  2. Blood biochemistry, serum creatinine (Cr) ≤ 1.5× upper limit of normal (ULN) or creatinine clearance ≥60 mL/min;Serum albumin ≥2.8g/dL, for patients with poor nutritional status before neoadjuvant therapy, patients who met the requirements through parenteral nutrition could also be included in the group;Total bilirubin (TBIL) ≤ 1.5×ULN;Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤2.5×ULN;

Exclusion Criteria:

• 1. Pregnant or lactating women;
• Patients with a known history of allergy to any investigative drug, similar drug or excipient;
• Patients with risk of massive gastrointestinal bleeding or gastrointestinal obstruction;
• Patients with a history of thromboembolism, except thrombosis caused by PICC;
• There are patients with active infection;
• Patients with unmanageable hypertension (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90mmHg);
• Patients with brain metastases with clinical symptoms or imaging evidence;
• Contraindications exist in treatment with other chronic diseases;
• Patients with a history of immunotherapy-related myocarditis, pneumonia, colitis, hepatitis, nephritis, etc., with current AE ≥ grade 2;
• According to the evaluation criteria of NCI CTCAE version 5.0, there are patients with all kinds of toxicities ≥ grade 2 due to previous treatment;
• Other conditions that the researchers determined were not suitable for inclusion in the study.
• Received any antitumor therapy and participated in other clinical studies within 4 weeks before enrollment.

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: SBRT followed by tislelizumab plus cetuximab and irinotecan	Drug: Tislelizumab; Tislelizumab will be administered on day 1 of each cycle at 200mg once every 14 days.; Drug: Irinotecan Hydrochloride; Irinotecan will be administered on day 1 of each cycle at 180 mg/m2 once every 14 days.; Drug: cetuximab; cetuximab will be administered on day 1 of each cycle at 500 mg/m2 once every 14 days.; Radiation: SBRT; 8-10Gy×5F，QOD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR	From enrollment to 12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival(PFS)	PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first	From enrollment to 12 month
Overall Survival (OS)	Overall Survival (OS), defined as the time from the date of randomization to the date of death, regardless of the cause of death.	From enrollment to 12 month

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 5, 2023
• Primary Completion (Anticipated): April 5, 2024
• Study Completion (Anticipated): April 5, 2025

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): April 5, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: STEC

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