Short-course Radiotherapy Followed by AK112 and CAPOX as Neoadjuvant Therapy for Locally Advanced Rectal Cancer

NCT06802666 | Recruiting Phase 2

• 1 other identifier: AK112-IIT-C-S-0010
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy and safety of short-course radiotherapy followed by AK112 in combination with CAPOX as neoadjuvant therapy in patients with locally advanced rectal cancer

Conditions

Locally Advanced Rectal Cancer; Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response rate (pCR)

  Pathological complete response will be made based on assessment of the surgical specimen at the primary treatment site，the absence of any viable tumor cells in the resected primary tumor specimen and all regional lymph node samples.

  though 19 weeks neoadjuvant treatment，after surgery completed

Secondary Outcomes (8)

• 3-years Event-Free Survival rate

  3 years

• OS

  From date of randomization until date of death from any cause，up to 3 years

• R0 resection rate

  From date of surgry，up to 1month

• AE

  up to 3 years

• 30-day postoperative mortality rates

  30 days post surgery

Study Arms (1)

SCRT+AK112+chemotherapy

EXPERIMENTAL

short-course radiotherapy followed by sequential chemotherapy and AK112

Radiation: short-course radiotherapy; Drug: Ivonescimab; Drug: capecitabine; Drug: oxaliplatin; Procedure: TME surgery

Interventions

short-course radiotherapy RADIATION

Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with AK112 regimen for 6 cycles.

Also known as: SCRT

SCRT+AK112+chemotherapy

Ivonescimab DRUG

AK112 20 mg/kg, intravenous infusion every 3 weeks (Q3W)

Also known as: AK112

SCRT+AK112+chemotherapy

capecitabine DRUG

1000mg/m2, bid, po, d1-14,q3w

SCRT+AK112+chemotherapy

oxaliplatin DRUG

130mg/m2, ivgtt, d1,q3w

SCRT+AK112+chemotherapy

TME surgery PROCEDURE

The surgery was performed 1 week after the end of neoadjuvant therapy.

SCRT+AK112+chemotherapy

Eligibility Criteria

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

You may qualify if:

• The subjects voluntarily joined this study, were able to complete the signing of the informed consent form, and had good compliance；
• Age ≥18 years and ≤75 years, without gender restriction.
• Histopathologically confirmed locally advanced rectal adenocarcinoma.
• Participants who are not suitable for standard therapy due to intolerable toxicity, lack of standard therapy, or refusal of standard therapy.
• Hematological parameters at baseline\* (within 7 days prior to the first dose of study drug) must meet the following criteria: • Hemoglobin ≥90 g/L • Absolute neutrophil count (ANC) ≥1.5×10\^9/L • Platelet count ≥100×10\^9/L • Eosinophils ≤1.5×upper limit of normal (ULN). \*Participants may not have received blood products (including red cell suspensions, plateletpheresis, cryoprecipitate), erythropoietin, or colony-stimulating factor supportive treatment within 7 days prior to blood sampling.
• Coagulation tests at baseline (within 7 days prior to the first dose) must meet the following criteria: • International normalized ratio (INR) ≤1.5×ULN (≤3×ULN if on stable anticoagulant therapy). • Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN (≤3×ULN if on stable anticoagulant therapy).
• Urinalysis at baseline (within 7 days prior to the first dose) must meet the following criteria: urine protein (UPRO) \<2+ or 24-hour urinary protein \<1 g.
• At least one measurable lesion according to RECIST v1.1 (solid tumors) criteria.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Expected survival ≥3 months.
• Women of childbearing potential and male participants with female partners of childbearing potential must agree to use effective contraception throughout the treatment period and for 6 months after the end of treatment.

You may not qualify if:

• Participants who have previously received immunotherapy, including immune checkpoint inhibitors (such as anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-TIGIT antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), or any other treatments targeting tumor immunological mechanisms, such as immune cell therapy.
• Pregnant or breastfeeding women, or women planning to become pregnant during the period from before the administration of the study drug, during treatment, or up to 6 months after the last dose.
• Known history of active epilepsy, active central nervous system (CNS) metastases, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, or new onset of brain or leptomeningeal metastases.
• Significant cardiovascular diseases of clinical importance.
• History of allergic constitution, asthma, or atopic dermatitis.
• Participants with large pleural effusion or ascites.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroid hormone, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Participants known or suspected to be allergic to the investigational product or any of its excipients.
• Participants with a history of significant toxicities associated with prior administration of immune checkpoint inhibitors or treatment with bevacizumab/pirfenidone-like agents that required permanent discontinuation of such treatment.
• Participants with unresolved toxicity \> Grade 1 related to any prior anticancer therapy (excluding persistent alopecia Grade 2, peripheral neuropathy, anemia, or hypomagnesemia).
• Active uncontrolled bleeding or known bleeding diathesis, serious non-healing wounds, ulcers, or bone fractures, such as esophageal or gastric varices requiring immediate intervention (e.g., band ligation or sclerotherapy), or signs of portal hypertension where the Investigator believes the risk of bleeding is high.
• Participants with a history of bowel obstruction (excluding those who have undergone curative surgery or have had complete resolution) or gastrointestinal perforation risk within 28 days prior to the first dose of this study (including but not limited to acute diverticulitis, abdominal abscess, peritoneal carcinomatosis, history of gastrointestinal perforation and/or fistula within 6 months prior to study entry).
• Current or recent (within 6 months) major gastrointestinal diseases or conditions in participants, including:
• Clinically significant history of gastrointestinal bleeding.

Sponsors & Collaborators

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

Study Sites (1)

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

Hubei, China

RECRUITING

MeSH Terms

Interventions

Capecitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Tao Zhang, MD

  Union Hospital affiliated to Tongji Medical College of Huazhong University ofScience and Technology

  STUDY DIRECTOR

Central Study Contacts

tao Zhang, MD

CONTACT

02785871982; 1277577866@qq.com

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: Director

Model Details: single arm

Study Record Dates

• First Submitted: January 18, 2025
• First Posted: January 31, 2025
• Study Start: October 16, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)