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

NCT06195670 | Not Yet Recruiting Phase 1

• 1 other identifier: HMPL-013-FLAG-C124
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

CRC; Metastatic Colorectal Cancer; Metastatic Colorectal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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)

• Overall Survival OS)

  From randomization until disease progression (up to approximately 3-5 years)

Study Arms (2)

SCRT + fruquintinib + sintilimab

EXPERIMENTAL

Drug: Experimental

Bevacizumab + Capecitabine

ACTIVE COMPARATOR

Drug: Active Comparator

Interventions

Experimental DRUG

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.

Also known as: SCRT + fruquintinib + sintilimab

SCRT + fruquintinib + sintilimab

Active Comparator DRUG

Capecitabine: bid po, 1000mg/m², on days 1-14, q3w; Bevacizumab: intravenous infusion, 7.5mg/kg, on day 1, q3w.

Also known as: Bevacizumab + Capecitabine

Bevacizumab + Capecitabine

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have signed an informed consent;
• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Ji Zhu

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; sintilimab; Bevacizumab; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ji Zhu, M.D.

CONTACT

0571-88128142 ext +86; leozhu@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 8, 2024
• Study Start: January 1, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 8, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)