Short-course Radiotherapy Followed by Fruquintinib Plus Adebrelimab and CAPOX in the Full Course Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Multicenter, Single-arm, Open-label Study

NCT06234007 | Recruiting Phase 2

• 1 other identifier: HMPL-013-FLAG-C128
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the efficacy and safety of short-course radiotherapy sequential fruquintinib in combination with adebrelimab and CAPOX (full course neoadjuvant therapy) in patients with locally advanced rectal cancer.

Conditions

Locally Advanced Rectal Cancer

Keywords

Neoadjuvant; Fruquintinib; Colorectal cancer

Outcome Measures

Primary Outcomes (1)

• pathology complete response(pCR)

  The proportion of subjects with no residual viable tumor cells(ypT0N0) in the primary tumor and lymph nodes, also defined as the proportion of subjects with grade 0 in the AJCC Tumor Regression Grading (TRG) scoring system(version 8.0).

  up to 6 months

Secondary Outcomes (4)

• 3-year Event-Free Survival(EFS) rate

  up to 36 months

• Overall Survival(OS)

  up to 36 months

• R0 resection rate

  up to 6 months

• Adverse events (AEs)

  up to 36 months

Study Arms (1)

SCRT followed by fruquintinib plus adebrelimab and CAPOX

EXPERIMENTAL

Drug: Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine

Interventions

Fruquintinib, Adebrelimab, Oxaliplatin, Capecitabine DRUG

Safety run-in phase: Fruquintinib 4mg/d, oral, once daily, continuous treatment for 2 weeks, 1 week off, q3w, 6 cycles; If the number of patients experiencing dose-limiting toxicity (DLT) was ≤1, the study would continue at that dose level. If the number of patients with DLTs was \>1, the dose of fruquintinib was decreased to 3mg/d, qd po, d1-14, q3w, and the dose expansion phase was continued；Adebrelimab 1200mg, d1, IV infusion, q3W, 6 cycles; Capecitabine 1000 mg/m2, twice a day, po, d1-14, followed by 7 days of rest, q3W, 6 cycles; Oxaliplatin 130 mg/m2, d1, q3W, 6 cycles; Dose expansion phase: Fruquintinib RP2D, qd po, d1-14, q3w, 6 cycles; Adebrelimab 1200mg, d1, IV infusion, q3W, 6 cycles; Capecitabine 1000 mg/m2, twice a day, po, d1-14, followed by 7 days of rest, q3W, 6 cycles; Oxaliplatin 130 mg/m2, d1, q3W, 6 cycles;

SCRT followed by fruquintinib plus adebrelimab and CAPOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent and volunteered to participate in the study;
• Age 18-75 years old (including the cut-off value), male or female;
• Locally advanced rectal adenocarcinoma confirmed by histopathology;
• High risk on pelvic MRI \[one of the following criteria\] :
• Clinical tumor (cT) stage cT4a or cT4b (according to the AJCC, 8th edition)
• Extramural vascular infiltration
• Clinical lymph node (cN) stage cN2 (according to the AJCC, 8th edition)
• Involvement of the mesenteric fascia
• Enlarged lateral lymph nodes
• The distance between the lower edge of the tumor and the anal edge is ≤10cm;
• Able to swallow tablets and capsules normally;
• ECOG PS 0-1
• Have not received any anti-tumor treatment for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
• Plan to undergo surgery after completion of total neoadjuvant therapy;
• No surgical contraindications;

You may not qualify if:

• Previous allergic history to any anti-angiogenesis targeted drug, any component of monoclonal antibody, capecitabine, oxaliplatin, or other platinum drugs;
• Have received or are receiving any of the following:
• being treated with an immunosuppressive drug, or systemic hormone, for immunosuppression within 2 weeks before the first dose of the study drug (dose\> 10mg/ day prednisone or equivalent); Inhaled or topical steroid use and dosage are allowed in the absence of active autoimmune disease; Prednisone 10mg/ day or equivalent dose of adrenocortical hormone replacement;
• received live attenuated vaccine within 4 weeks before the first dose of study drug;
• major surgery or severe trauma within 4 weeks before the first dose of study drug;
• A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
• The presence of uncontrolled cardiac symptoms or diseases, including but not limited to: (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias without or poorly controlled after clinical intervention; (5) patients with hypertension that is not well controlled with a single antihypertensive drug (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100mmHg), or patients using two or more antihypertensive drugs to control blood pressure; (6) New York Heart Association (NYHA) functional class \&gt; Grade II or left ventricular ejection fraction (LVEF) \< 50%;
• Severe infection (CTCAE \> 2) occurred within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; Prophylactic antibiotics were excluded if there was active pulmonary inflammation on baseline chest imaging, if there were signs and symptoms of infection within 14 days before the first dose of study drug, or if oral or intravenous antibiotics were required;
• Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive, and HCV RNA above the detection limit of the analytical method);
• The patient had a second primary malignancy;
• Pregnant or lactating women;
• History of arterial/venous thrombosis events within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism;
• Persons with a history of psychotropic drug abuse and inability to quit or with mental disorders;
• Patients with any constitutional sign or history of bleeding regardless of severity;

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Renmin Hospital of Wuhan University: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; Oxaliplatin; 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)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Tao Zhang, Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• KaiXiong Tao, Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

zhenyu Lin, Ph.D

CONTACT

+8615827130393; whxhlzy@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: January 31, 2024
• Study Start: December 1, 2023
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)