Clinical Study of Short-course Radiotherapy Followed by Fruquintinib Plus Sintilimab vs Bevacizumab Plus Capecitabine as First Line Treatment in Advanced mCRC

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer; Metastatic Colorectal Adenocarcinoma; CRC
• Intervention / Treatment: Drug: Experimental; Drug: Active Comparator

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.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ji Zhu, M.D.; Phone Number: 0571-88128142 ext +86; Email: leozhu@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Ji Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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;
• Hemoglobin ≥ 8g/dL;
• Total bilirubin<1.5 times ULN;
• ALT and AST<2.5 times ULN (liver metastasis patients<5 times ULN);
• Serum creatinine ≤ 1.5 times ULN;
• Endogenous creatinine clearance rate>50ml/min;
• International standardized ratio (INR) of coagulation function ≤ 1.5 × ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
• Women of childbearing age or men whose partners have a desire to conceive should take effective contraceptive measures.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCRT + fruquintinib + sintilimab	Drug: Experimental; SCRT: 5*5Gy for 5 days, after a one-week rest, with fruquintinib plus sintilimab followed; Fruquintinib: qd po, 4mg/d, 2weeks on/1 week off, q3w; Sintilimab: intravenous infusion, 200mg, on day 1, q3w.; Other Names: SCRT + fruquintinib + sintilimab
Active Comparator: Bevacizumab + Capecitabine	Drug: Active Comparator; Capecitabine: bid po, 1000mg/m², on days 1-14, q3w; Bevacizumab: intravenous infusion, 7.5mg/kg, on day 1, q3w.; Other Names: Bevacizumab + Capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b - Objective Response Rate (ORR)	ORR according to RECIST v1.1, as assessed by the Investigator	From randomization until disease progression (up to approximately 3-5 years)
Phase 2 - Progression-free Survival (PFS)	PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator	From randomization until disease progression (up to approximately 3-5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and safety of study regimens	Number of Participants With Treatment-emergent Adverse Events (TEAEs) according to CTCAE v5.0	From randomization until the end of treatment (up to approximately 3-5 years)
Disease Control Rate (DCR)	DCR according to RECIST v1.1, as assessed by the Investigator	From randomization until disease progression (up to approximately 3-5 years)
Overall Survival OS)	OS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator	From randomization until disease progression (up to approximately 3-5 years)

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Ji Zhu, M.D., Zhejiang Cancer Hospital; Principal Investigator: Zhong Shi, M.D., Zhejiang Cancer Hospital; Principal Investigator: Wangxia Lv, M.D., Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Estimated): January 8, 2024

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: HMPL-013-FLAG-C124

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