Trial Title:
AK104 Combined With I-125 Brachytherapy for Recurrent or Metastatic Cervical Cancer
NCT ID:
NCT06062589
Condition:
Cervical Cancer
Conditions: Official terms:
Uterine Cervical Neoplasms
Study type:
Observational
Overall status:
Not yet recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Radiation
Intervention name:
Iodine-125 particle brachytherapy
Description:
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.
Intervention type:
Drug
Intervention name:
AK104
Description:
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.
Other name:
Cadonilimab
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.
Detailed description:
Study Title AK104 combined with Iodine-125 brachytherapy in the Treatment of Recurrent or
Metastatic Cervical Cancer
Study Objectives Primary Objective To explore the effectiveness of AK104 in combination
with Iodine-125 brachytherapy in the treatment of recurrent or metastatic cervical
cancer.
Secondary Objective To explore the safety of AK104 in combination with Iodine-125
brachytherapy in the treatment of recurrent or metastatic cervical cancer.
Study Endpoints Primary Endpoint Objective response rate (ORR) based on RECIST 1.1
evaluation.
Secondary Endpoints Disease control rate (DCR), progression-free survival (PFS), and
3-year overall survival rate (OS) based on RECIST 1.1 evaluation.
Safety assessment: Incidence and severity of adverse events (AE), clinically significant
abnormal laboratory test results.
Target 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).
Study Drug and Administration AK104, 6mg/kg Q2W, administered via intravenous infusion
over 60 minutes (±10 minutes). For subjects unable to tolerate a 60-minute infusion, the
infusion time may be extended up to 120 minutes. Dose adjustments are not allowed during
treatment with AK104, but treatment may be delayed for a maximum of 12 weeks from the
previous dose. Treatment will be discontinued if AK104 has been withheld for more than 12
weeks due to treatment-related immune-related adverse events (irAE) requiring
corticosteroid therapy, or for reasons unrelated or potentially unrelated to AK104, but
the investigator determines that the patient would benefit from continued treatment after
discussion with the medical monitor.
Criteria for eligibility:
Study pop:
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).
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
1. 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).
2. Pathologically and radiologically confirmed tumor with maximum diameter not
exceeding the maximum diameter for particle treatment (5-7cm).
3. Age ≥18 years and ≤70 years, female at the time of signing the informed consent.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, able to tolerate
puncture.
5. Measurable lesions according to RECIST 1.1, with target lesions unsuitable for
surgical treatment.
6. Expected survival time of more than 3 months.
7. 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
- Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN); if abnormal,
investigate T3 and T4 levels, and if T3 and T4 levels are normal, the patient
may be eligible.
8. Female subjects of childbearing potential must have a negative serum pregnancy test
within 3 days before starting study drug and agree to use a medically acceptable
method of contraception during the study and for 3 months after the last dose of
study drug.
9. Signed informed consent and the subject must understand the purpose of the study and
the requirements for participation and voluntarily agree to participate.
Exclusion Criteria:
Potential subjects who meet any of the following criteria should be excluded from the
study:
1. 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.
2. Diagnosis of any other malignant tumor within the past 3 years.
3. Use the first dose, excluding intranasal and inhaled corticosteroids or physiologic
doses of systemic corticosteroids (not exceeding 10 mg/day prednisolone or
equivalent).
4. 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.
5. 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.
6. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg or diastolic blood
pressure ≥90 mmHg despite optimal medical management).
7. 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.
8. 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.
9. 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.
10. 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.
11. History of substance abuse, inability to discontinue substance abuse or presence of
psychiatric disorders.
12. Major surgery within 4 weeks before the first dose or presence of open wounds or
fractures.
13. 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.
14. Urinalysis showing urine protein ≥++, or confirmed 24-hour urine protein ≥1.0 g.
15. Human immunodeficiency virus (HIV) infection or known acquired immune deficiency
syndrome (AIDS), active hepatitis B (HBV DNA ≥500 IU/ml), hepatitis C (positive HCV
antibodies and HCV-RNA above the detection limit of the assay), or concurrent
infection with both hepatitis B and hepatitis C.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
October 11, 2023
Completion date:
October 11, 2027
Lead sponsor:
Agency:
Peking University Third Hospital
Agency class:
Other
Source:
Peking University Third Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06062589
