SBRT-LDRT-Cadonilimab for Advanced Gastric, Colorectal and Ovarian Cancers With Peritoneal Metastases

NCT06940921 | Active Not Recruiting Phase 1

• 1 other identifier: Zhang Tao
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to see if high- and low-dose radiotherapy combined with immunotherapy can work in patients with advanced gastric, colorectal, and ovarian cancers with peritoneal metastases, and to learn about the safety of this new combination treatment modality. The main questions they aim to answer are:

• Can whole-abdominal low-dose radiotherapy (LDRT) combined with selected-site stereotactic body radiation therapy (SBRT) followed by Cadonilimab control peritoneal lesions and malignant ascites in patients with advanced solid tumors with peritoneal metastases?
• Can the novel treatment modality of high- and low-dose radiotherapy combined with immunotherapy produce a survival benefit in patients with advanced gastric, colorectal, and ovarian cancers who have received multiple lines of therapy?
• Is the safety profile of this new treatment modality acceptable? Participants will:
• Receive stereotactic body radiation therapy (SBRT) to selected sites and low-dose radiotherapy (LDRT) to the whole abdomen, followed by bi-weekly treatment with Cadonilimab until disease progression, death, toxicity intolerance or withdrawal of informed consent.
• Receive whole body imaging and laboratory tests every 6-8 weeks to assess the efficacy of tumor treatment.

Conditions

Advanced Gastric Cancer; Advanced Colorectal Cancer; Advanced Ovarian Cancer; Peritoneal Metastasis

Keywords

low-dose radiation therapy; stereotactic body radiation therapy; Cadonilimab; peritoneal metastasis; gastric cancer; colorectal cancer; ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Peritoneal response rate

  The Peritoneal Cancer Index (PCI) score is currently the most commonly used and validated tool for assessing the extent of peritoneal metastasis and prognosis. The method is to divide the abdominal cavity into 9 partitions, the small intestine into 4 partitions, a total of 13 partitions, and each partition is assigned a score of 0\~3 according to the lesion size (LS) seen intraoperatively. That is, the LS score for each of the 13 divisions was determined by intraoperative or radiologic imaging, with a total score of 39 points. In this study, imaging evaluations were performed every 8 weeks to assess the efficacy of peritoneal tumor lesions by abdominal DWI + T2 MRI or abdominal CT enhancement. PCI scores ranged from 0\~39, with higher scores implying more peritoneal metastatic lesions. The peritoneal response was evaluated as effective if the PCI score decreased compared with baseline, stable if the PCI score remained unchanged, and ineffective if the PCI score increased.

  within 3 years after primary treatment

Secondary Outcomes (6)

• Objective response rate (ORR)

  within 3 years after primary treatment

• Disease Control Rate (DCR)

  within 3 years after primary treatment

• Duration of Response (DoR)

  within 3 years after primary treatment

• Progression-free survival (PFS)

  within 3 years after primary treatment

• Overall Survival (OS)

  within 3 years after primary treatment

Study Arms (1)

Whole abdominal LDRT combined with SBRT followed by Cadonilimab group

EXPERIMENTAL

Patients in the experimental arm will receive stereotactic body radiation therapy (SBRT) to selected tumor sites and low-dose radiotherapy (LDRT) to the whole abdomen, followed by Cadonilimab immunotherapy.

Radiation: Low-Dose Radiation(LDRT) + Stereotactic body radiotherapy (SBRT); Drug: Cadonilimab

Interventions

Low-Dose Radiation(LDRT) + Stereotactic body radiotherapy (SBRT) RADIATION

Radiation: Stereotactic Body Radiation Therapy (SBRT) * Stereotactic Body Radiation Therapy (SBRT) will be performed first at a total dose of 20-50 Gy, delivered in 3-5 fractions of 6-10 Gy each. And the target area was specifically selected based on the location and size of the patient's tumor. Radiation: low-dose radiotherapy (LDRT) * Whole-abdominal low-dose radiotherapy will be initiated within 10 days of the end of SBRT with a total dose of 7-15 Gy at 0.5-2.0 Gy twice daily. And the target area included all suspicious tumor tissues and potential metastatic foci in the abdominal cavity.

Whole abdominal LDRT combined with SBRT followed by Cadonilimab group

Cadonilimab DRUG

· Cadonilimab: 6 mg/kg IV, D1, Q2W, until disease progression, death, toxicity intolerance or withdrawal of informed consent

Whole abdominal LDRT combined with SBRT followed by Cadonilimab group

Eligibility Criteria

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

You may qualify if:

• With his/her own consent and signed Informed Consent Form (ICF), willingness and ability to comply with planned visits, study treatments, laboratory tests and other experimental procedures.
• At the time of signing the ICF, the subject must be ≥ 18 years of age with a life expectancy of ≥ 12 weeks.
• Gastric, colorectal, or ovarian cancer diagnosed by pathologic histology or cytology. And accompanied by peritoneal metastasis confirmed by pathohistology or cytology or imaging (CT/MRI/PET-CT).
• Advanced or metastatic gastric cancer, colorectal cancer, ovarian cancer (AJCC/UICC stage IV) confirmed by imaging of the chest, abdomen and pelvis (CT/MRI/PET-CT).
• Previously received multiple lines of systemic antitumor therapy, no longer available or refused standard treatment.
• At least 1 measurable lesion other than the lesion to be treated with SBRT according to RECIST 1.1 criteria. For lesions that have received prior radiotherapy, only a definite progression of that lesion is considered a measurable lesion.
• An Eastern Cooperative Oncology Group physical status score (ECOG) of 0-1.
• Appropriate organ function based on the following laboratory test values obtained during the Screening Period: white blood cell count ≥ 3 x 109/L, neutrophil count ≥ 1.5 x 109/L, platelet count 75 x 109/L; serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase or ≤ 2.5 x UNL (hepatic metastasis) subjects should be ≤ 5 x ULN), serum creatinine ≤ 1.5 x UNL.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 3 days prior to study entry and be willing to use a medically approved, highly effective contraceptive such as an IUD, birth control pills, or condoms for the duration of the study and for 3 months after the last dose of study drug. For male subjects whose partner is a female of childbearing age, they should be surgically sterilized or agree to use an effective method of contraception for the duration of the study and for a period of 3 months after the final study drug administration.
• No concurrent participation in other clinical trials during the study period.

You may not qualify if:

• Previous or concurrent other active malignant tumors. Except for malignant tumors that have received curative treatment and have been free of disease for more than 5 years or carcinoma in situ that can be cured by adequate treatment.
• Current gastrointestinal diseases such as duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions that may cause bleeding or perforation of the gastrointestinal tract as determined by the investigator.
• Other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator.
• Thrombotic or embolic events, such as cerebrovascular accident, pulmonary embolism, deep vein thrombosis, have occurred within 12 months prior to enrollment.
• Myocardial infarction, severe/unstable angina pectoris, NYHA class 2 or higher cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmia, and symptomatic congestive heart failure.
• Systemic antibiotic use for ≥ 7 days within 4 weeks prior to enrollment in the study or unexplained fever \> 38.5°C during screening/prior to first dose will be excluded. Fever due to oncologic causes may be enrolled at the discretion of the investigator.
• presence of any prior treatment-induced, unabated adverse events Common Terminology Criteria (NCI CTCAE Version 5.0) Grade 2 or greater toxicity, excluding anemia, alopecia, and skin pigmentation.
• history of idiopathic pulmonary fibrosis, opportunistic pneumonia, drug-induced pneumonia, or idiopathic pneumonia, or evidence of active pneumonia, active tuberculosis on chest computed tomography scan at screening.
• Human Immunodeficiency Virus (HIV) infection or known Acquired Immune Deficiency Syndrome (AIDS), untreated active hepatitis (Hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; and Hepatitis C, defined as HCV-RNA above the lower limit of detection of the analytical method) or combination of Hepatitis B and Hepatitis C co-infection.
• symptomatic, untreated, or active progressive central nervous system (CNS) metastases Patients with CNS lesions treated and asymptomatic are eligible for this study if they meet all of the following criteria: measurable lesions exist outside the CNS as defined by RECISTv1.1; the patient does not have a history of intracranial hemorrhage or intraspinal hemorrhage; and the patient has not received stereotactic radiotherapy within the last 7 days prior to the start of study treatment. days prior to the start of study treatment; patients have not received stereotactic radiotherapy within 14 days prior to the start of study treatment, whole-brain radiotherapy within 14 days prior to the start of study treatment, or neurosurgical resection within days prior to the start of study treatment; and patients do not need to be on continuous corticosteroid therapy for CNS disease.
• Presence of an active or previous autoimmune disease or immunodeficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis. Exceptions are: patients with a history of autoimmune hypothyroidism who are receiving thyroid replacement therapy are eligible; patients with type I diabetes mellitus who are receiving an insulin regimen and are in glycemic control are eligible; patients with eczema, psoriasis, chronic lichen simplex, or vitiligo with only cutaneous symptoms are eligible if all of the following criteria are met: the rash must cover \< 10% of body surface area; good disease control at baseline and require only topical weak corticosteroid therapy; and no acute exacerbation of the underlying disease within the past 12 months.
• have used systemic immunosuppressive medications within 2 weeks prior to the start of study treatment or anticipate the need for systemic immunosuppressive medications during study treatment, with the following exceptions: patients receiving short-term, low-dose systemic immunosuppressive medications or patients receiving a one-time pulse of systemic immunosuppressive medications may be eligible to participate in this study after obtaining confirmation of their participation from the Medical Monitor; patients receiving salt corticosteroids, inhaled or low-dose corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD) or asthma, or patients receiving low-dose corticosteroids for the treatment of upright hypotension or adrenal insufficiency are eligible to participate in this study.
• known or suspected history of allergy to any of the relevant drugs used in the study.
• Pregnant or lactating women.
• Women of childbearing age or men of childbearing potential who are not using or refuse to use an effective non-hormonal contraceptive.

Sponsors & Collaborators

• Zhang Tao: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Study Sites (1)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

MeSH Terms

Conditions

Stomach Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zhang Tao, PhD

  First Affiliated Hospital of Chongqing Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: April 23, 2025
• Study Start: March 20, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)