AK104 Combined With I-125 Brachytherapy for Recurrent or Metastatic Cervical Cancer

NCT06062589 | Not Yet Recruiting

• 1 other identifier: M2023109
• Study Type: observational
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this study is to determine efficacy and safety of AK104 combined with I-125 brachytherapy for recurrent or metastatic cervical cancer. This is an open-label, single-center, observational study of AK104 with Iodine-125 brachytherapy in the treatment of recurrent or metastatic cervical cancer. 18 eligible patients will receive Iodine-125 brachytherapy (single implantation, half-life of 60 days, 99% of total dose given after 90 days), followed by AK104 treatment (6mg/kg Q2W) starting within 1 week of particle implantation, for a total of 6 cycles or until disease progression, intolerable toxicity, investigator decision, withdrawal of informed consent, death, or other reasons as specified in the protocol.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR was assessed by the site Investigator using RECIST 1.1 and was defined as the percentage of patients with a confirmed overall response of CR or PR

  From Baseline to 3 months

Secondary Outcomes (4)

• Disease control rate (DCR)

  From Baseline to 2 years]

• Progression-free survival (PFS)

  From Baseline to 2 years]

• Overall survival rate (OS)

  : From Baseline to 3 years]

• The adverse events

  From Baseline to 2 years

Interventions

Iodine-125 particle brachytherapy RADIATION

All enrolled patients' relapsed or metastatic lesions underwent image-guided radiation I-125 particle implantation brachytherapy (single implantation, half-life of 60 days, 99% of total dose given after 90 days). The prescribed dose is above 130Gy. Technical process: positioning and preoperative planning design; Template reset and particle implantation under the guidance of image system; Rapid and real-time intraoperative optimization; Postoperative dose validation.

AK104 DRUG

AK104 treatment (6mg/kg Q2W) starting within 1 week of particle implantation, for a total of 6 cycles or until disease progression, intolerable toxicity, investigator decision, withdrawal of informed consent, death, or other reasons as specified in the protocol.

Also known as: Cadonilimab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with unresectable recurrent or metastatic cervical cancer who have undergone radical surgery and/or radical chemoradiotherapy and are suitable for local radiotherapy (non-central pelvic recurrence or oligometastasis in stage IVB).

You may qualify if:

• Histologically or cytologically confirmed cervical cancer, with recurrence or metastasis after previous systemic surgery, postoperative chemoradiotherapy, or radical chemoradiotherapy, and suitable for local radiotherapy (non-central pelvic recurrence or oligometastasis in stage IVB).
• Pathologically and radiologically confirmed tumor with maximum diameter not exceeding the maximum diameter for particle treatment (5-7cm).
• Age ≥18 years and ≤70 years, female at the time of signing the informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1, able to tolerate puncture.
• Measurable lesions according to RECIST 1.1, with target lesions unsuitable for surgical treatment.
• Expected survival time of more than 3 months.
• Adequate organ function as per standard criteria for immunotherapy:
• Absolute neutrophil count (ANC) ≥1.5×109/L
• Platelets ≥75×109/L
• Hemoglobin ≥90 g/L
• Serum albumin ≥30 g/L
• Total bilirubin (TBil) ≤1.5×ULN
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5×ULN; if there is liver metastasis, ALT and AST \<5×ULN
• Serum creatinine ≤1.5×ULN
• Blood urea nitrogen (BUN) ≤2.5×ULN

You may not qualify if:

• Potential subjects who meet any of the following criteria should be excluded from the study:
• History of using anti-PD-1 antibodies, anti-CTLA-4 antibodies, TCR-T, CAR-T, or other immunotherapy within the past 4 weeks before the first dose, or participation in other anti-tumor drug clinical trials within the past 4 weeks before the first dose, or planned use of attenuated live vaccines during the study period.
• Diagnosis of any other malignant tumor within the past 3 years.
• Use the first dose, excluding intranasal and inhaled corticosteroids or physiologic doses of systemic corticosteroids (not exceeding 10 mg/day prednisolone or equivalent).
• Patients with symptomatic, visceral metastasis, or short-term life-threatening complications risk, including uncontrollable large effusions (pleural, pericardial, or peritoneal), lymphangitis carcinomatosis, and 30% or more liver involvement.
• Presence of any active autoimmune disease or history of autoimmune disease, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism. Patients with vitiligo or childhood asthma that has been completely resolved without any intervention during adulthood can be included. Patients with asthma requiring bronchodilators for medical intervention cannot be included.
• Uncontrolled hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg despite optimal medical management).
• Grade II or higher myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥450 ms for males or ≥470 ms for females), NYHA class III-IV heart failure, left ventricular ejection fraction (LVEF) \<50% as determined by echocardiography. Patients who experienced myocardial infarction, New York Heart Association class II or higher heart failure, uncontrolled angina, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or acute ischemia or active conduction system abnormalities based on electrocardiogram within 6 months before enrollment.
• Coagulation abnormalities (INR \>1.5 or prothrombin time (PT) \> upper limit of normal (ULN) + 4 seconds or APTT \>1.5 ULN), bleeding tendency, or receiving thrombolysis or anticoagulation therapy.
• Presence of obvious hemoptysis or expectoration of at least half a teaspoon (2.5 ml) of blood within 2 months before enrollment; or occurrence of significant clinically relevant bleeding symptoms or clear bleeding tendency, such as gastrointestinal bleeding, bleeding gastric ulcer, baseline occult blood++ in stool, or vasculitis within 3 months before enrollment; or occurrence of arterial/venous thromboembolic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, or cerebral infarction), deep vein thrombosis, or pulmonary embolism within 6 months before enrollment.
• Severe infection within 4 weeks before the first dose (e.g., requiring intravenous administration of antibiotics, antifungals, or antiviral agents), or unexplained fever \>38.5°C during screening or within 4 weeks before the first dose.
• History of substance abuse, inability to discontinue substance abuse or presence of psychiatric disorders.
• Major surgery within 4 weeks before the first dose or presence of open wounds or fractures.
• Factors significantly affecting oral drug absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction; or occurrence of fistula or perforation of hollow organs within 6 months.
• Urinalysis showing urine protein ≥++, or confirmed 24-hour urine protein ≥1.0 g.

Sponsors & Collaborators

• Peking University Third Hospital: lead

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Ping Jiang

CONTACT

13439796018; drjiangping@qq.com

Xiuwen Deng

CONTACT

15811123680; justshowen@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 2, 2023
• Study Start: October 11, 2023
• Primary Completion: January 11, 2025
• Study Completion (Estimated): October 11, 2027
• Last Updated: October 2, 2023

Record last verified: 2023-07