Oral Chemotherapy, Targeted Therapy and Immunotherapy With/Without Radiotherapy as 3rd- or Later-line Therapy for Advanced MSS/pMMR Colorectal Cancer

NCT06764680 | Recruiting Phase 2

• 1 other identifier: B2024-585-01
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The current phase 2, double cohort clinical trial was designed to determine the effectiveness of Trifluridine and Tipiracil Hydrochloride Tablets, Bevacizumab and Sintilimab with/without involved lesions irradiation as 3rd- or later-line therapy for advanced MSS/pMMR colorectal cancer.

Conditions

Colorectal Cancer Metastatic; Chemotherapy; Targeted Therapy; Immunotherapy; Radiotherapy, Intensity-Modulated

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate (ORR) was defined as the percentage of CR+PR among the patients who could be evaluated for efficacy.

  Baseline, 6-8 weeks after treatment complete

Secondary Outcomes (4)

• Disease control rate (DCR)

  Baseline, 6-8 weeks after treatment complete

• Progression-free survival (PFS)

  month 6, year 1, year 2

• Overall survival (OS)

  month 6, year 1, year 2

• Treatment related toxicity

  Baseline, 6-8 weeks after treatment complete

Study Arms (2)

three-drug combination

EXPERIMENTAL

trifluorouracil tepidopyrimidine, bevacizumab, and sindilizumab

Drug: Trifluorouracil tepidopyrimidine; Drug: Bevacizumab; Drug: Sindilizumab

three-drug combination and radiotherapy

EXPERIMENTAL

trifluorouracil tepidopyrimidine, bevacizumab, and sindilizumab combine with palliative radiotherapy of the lesions

Drug: Trifluorouracil tepidopyrimidine; Drug: Bevacizumab; Drug: Sindilizumab; Radiation: IMRT

Interventions

Trifluorouracil tepidopyrimidine DRUG

30mg/m2. P.O. bid. d1-d5 and d15-d19. q4w

three-drug combination; three-drug combination and radiotherapy

Bevacizumab DRUG

5mg/kg. ivgtt. d1 and d15. q4w

three-drug combination; three-drug combination and radiotherapy

Sindilizumab DRUG

200mg. ivgtt. d1. q4w

three-drug combination; three-drug combination and radiotherapy

IMRT RADIATION

In terms of obstruction, bleeding, compression, or pain due to a tumor that requires local treatment. IMRT was delivered to the involved lesions.

three-drug combination and radiotherapy

Eligibility Criteria

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

You may qualify if:

• patients with advanced colorectal adenocarcinoma of MSS/pMMR confirmed by histologic or cytologic diagnosis;
• aged 18 years and older;
• have a quality of life score of 0-1 according to the Eastern Cooperative Oncology Group (ECOG);
• can take oral medications;
• expected survival ≥ 3 months;
• progressed after standard second-line or more than second-line therapy (received oxaliplatin, irinotecan, and fluorouracil analogs);
• have a measurable target lesion according to RECIST v1.1 evaluation criteria;
• have a number of recurrent metastatic organs ≤ 2 for all measurable lesions, a maximum diameter of recurrent metastatic lesions ≤ 5 cm, and a total number of recurrent metastatic lesions ≤ 10;
• agree to provide previously stored tumor tissue specimens or perform biopsies to collect tumor lesion tissue for biomarker analysis
• have chest, abdomen and pelvis CT or whole body PET-CT results within 4 weeks before enrollment;
• no ascites;
• having adequate major organ function, electrocardiogram, blood, biochemistry and other basic tests to exclude contraindications to chemotherapy and radiotherapy;
• hemoglobin \>8g/L, platelets ≥100×10\^9/L, neutrophils ≥1.5×10\^9/L
• for patients with liver metastases, aminotransferases and bilirubin \< 5 times the upper limit of normal;
• for patients without liver metastases, aminotransferases and bilirubin should be \<2.5 times the upper limit of normal.

You may not qualify if:

• prior application of trefluridine tepidopyrimidine;
• prior application of PD-1 or PD-L1 monoclonal antibody;
• extensive bone metastases;
• extensive peritoneal metastases;
• malignant hydrothorax and ascites;
• clinical or imaging signs of spinal cord compression, or dural sac tumor visible on MRI within 2 mm of the spinal cord. If surgically resectable, it may be enrolled, but a maximum of 3 surgical sites are allowed;
• unstable brain metastases with clinical signs or imaging evidence that require surgical decompression;
• brainstem metastases;
• metastatic lesions invading any of the following structures: gastrointestinal tract (including esophagus, stomach, small intestine, large intestine), skin. Includes extensive/poppy metastatic disease (e.g., brain, bone, lung, liver), or other sites where an adequate dose of irradiation could not be given (e.g., lymphovascular dissemination, malignant pleural and abdominal fluid, molluscum contagiosum metastases);
• multiple intracranial metastases only;
• pregnant or lactating females;
• no reliable contraception during the reproductive period
• patients with a known history of hypersensitivity to any of the study drugs, analogs, or excipients;
• patients at risk of gastrointestinal hemorrhage or gastrointestinal obstruction;
• patients with a history of thromboembolism, with the exception of thrombosis caused by PICCs or infusion ports

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Weiwei Xiao, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weiwei Xiao, M.D.

CONTACT

+86 020 8734 0951; xiaoww@sysucc.org.cn

Liping Chen

CONTACT

+86 020 87340767; chenlp@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 8, 2025
• Study Start: December 31, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 24, 2025

Record last verified: 2024-11

Locations

CN (1)