An Open-label, Multi-centered, Two-stage Clinical Study of Short-course Radiotherapy Followed by Fruquintinib Plus Sintilimab vs Bevacizumab Plus Capecitabine in the First Line Treatment of Advanced mCRC Patients Unfit for Intense Therapy
Overview
- Phase
- Phase 1
- Intervention
- Experimental
- Conditions
- CRC
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 220
- Locations
- 1
- Primary Endpoint
- Phase 2 - Progression-free Survival (PFS)
- Status
- Not Yet Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The aim of this study is to evaluate the efficacy and safety of short course radiotherapy followed by fruquintinib combined with Sintilimab as the first-line treatment of advanced mCRC compared to bevacizumab combined with capecitabine in patients unfit for intensive therapy.
Detailed Description
Anti-angiogenic therapy combined with immune checkpoint inhibitors in advanced mCRC has shown promising efficacy with acceptable toxicities. Radiotherapy may reshape the tumor immune microenvironment, thereby improving the efficacy of subsequent anti angiogenic drugs combined with immunotherapy. The study is a prospective, multi-centered, two-stage clinical study with 220 unresectable advanced mCRC patients unfit for oxaliplatin or irinotecan-based intensive chemotherapy enrolled. In phase 1b, 20 patients will be recruited and the efficacy and safety of SCRT followed by fruquintinib plus sintilimab will be explored. In phase 2, 200 patients will be randomized and the efficacy and safety will be compared between SCRT followed by fruquintinib plus sintilimab and capecitabine plus bevacizumab.
Investigators
Ji Zhu
Professor
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Have signed an informed consent;
- •18 to 85 years old (including 18 and 85 years old);
- •Histopathologically confirmed unresectable advanced metastatic colorectal adenocarcinoma;
- •Have not received anti-tumor treatment for metastatic disease;
- •Inability to tolerate intensive treatment regimens based on oxaliplatin or irinotecan as determined by researchers;
- •At least one measurable lesion;
- •Expected life expectancy ≥ 12 weeks;
- •The function of important organs within the 14 days prior to enrollment meets the following requirements (no blood components or cell growth factors are allowed to be used within the 14 days prior to enrollment):
- •Neutrophil absolute count ≥ 1.5 × 10\^9/L;
- •Platelets ≥ 80 × 10\^9/L;
Exclusion Criteria
- •Currently has a disease or condition that affects drug absorption, or the patient is unable to take oral drugs;
- •Currently has digestive tract diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresectable tumors, or other conditions determined by the researcher that may cause gastrointestinal bleeding or perforation;
- •History of serious cardiovascular and cerebrovascular diseases;
- •Other malignant tumors within the past 5 years, excluding skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
- •Clinically uncontrolled active infection, such as acute pneumonia, active hepatitis B or hepatitis C (hepatitis B virus DNA ≥ 1 × 104 copies/mL or\>2000 IU/ml);
- •Currently has central nervous system (CNS) metastasis or has a history of unstable or clinically symptomatic brain metastasis;
- •Pregnant (positive pregnancy test before medication) or breastfeeding women;
- •Urine protein ≥ 2+, or 24-hour urine protein \>1.0g;
- •Histologically confirmed MSI-H/dMMR tumors;
- •Patients deemed unsuitable by the researchers for inclusion in this study.
Arms & Interventions
SCRT + fruquintinib + sintilimab
Intervention: Experimental
Bevacizumab + Capecitabine
Intervention: Active Comparator
Outcomes
Primary Outcomes
Phase 2 - Progression-free Survival (PFS)
Time Frame: From randomization until disease progression (up to approximately 3-5 years)
PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator
Phase 1b - Objective Response Rate (ORR)
Time Frame: From randomization until disease progression (up to approximately 3-5 years)
ORR according to RECIST v1.1, as assessed by the Investigator
Secondary Outcomes
- Overall Survival OS)(From randomization until disease progression (up to approximately 3-5 years))
- Tolerability and safety of study regimens(From randomization until the end of treatment (up to approximately 3-5 years))
- Disease Control Rate (DCR)(From randomization until disease progression (up to approximately 3-5 years))