Trial Title:
Phase II Study on Neoadjuvant Therapy of AK104 Combined With Nab-paclitaxel/Carboplatin in Fertility Preserving Surgery
NCT ID:
NCT06209294
Condition:
Neoadjuvant Immunotherapy
Cervical Cancer
Fertility-sparing Surgery
Conditions: Official terms:
Uterine Cervical Neoplasms
Paclitaxel
Carboplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AK104
Description:
AK104(10 mg/kg) d1,22
Arm group label:
Experimental: AK104 combined with nab-paclitaxel and carboplatin
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
AUC=2 d1,8,15,22, 29, 36
Arm group label:
Experimental: AK104 combined with nab-paclitaxel and carboplatin
Intervention type:
Drug
Intervention name:
Nab paclitaxel
Description:
125mg／m2 d1,8,15,22,29,36
Arm group label:
Experimental: AK104 combined with nab-paclitaxel and carboplatin
Summary:
This is a Phase II study of neoadjuvant therapy of AK104 combined with
nab-paclitaxel/carboplatin in fertility saving surgery for stage IB2-IB3 cervical cancer
(FIGO 2018). The main questions it aims to answer are:
- · Evaluate the safety of AK104 combined with nab-paclitaxel/carboplatin in the
neoadjuvant treatment of cervical cancer
- · Evaluate the tumor regression and Major Pathological Response(MPR) of AK104
combined with nab-paclitaxel/carboplatin as neoadjuvant therapy for cervical cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Voluntarily sign a written ICF.
- Age ≥ 18 years old and ≤ 45 years old at the time of enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Patients with histologically confirmed (2018 FIGO) stage IB2-IB3 cervical squamous
cell carcinoma, adenocarcinoma, and adenosquamous carcinoma.
- Imaging evaluation showed no distant metastasis or regional lymph node metastasis,
and the tumor was limited to the cervix.
- Have not received any systemic or local anti-tumor treatment for cervical cancer
before the first medication, including radiotherapy, chemotherapy, immunotherapy,
biological agents, small molecule targeted therapy, etc.
- Patients who require preservation of reproductive function and who are judged by the
researcher to have no contraindications to childbirth surgery.
- At least 1 untreated measurable lesion according to RECIST v1.1.
- Subjects agree to collect tumor tissue and peripheral blood samples required during
the screening period and research process and use them in related research.
- With good organ function:
a) Hematology (no blood components and cell growth factor support therapy were used
within 7 days before starting study treatment): i. Absolute neutrophil count ANC ≥
1.5 × 109/L (1,500/mm3); ii. Platelet count ≥ 100 × 109/L (100,000/mm3); iii.
Hemoglobin ≥ 90 g/L. b) Kidney: i. Calculated creatinine clearance* (CrCl) ≥ 50
mL/min
* CrCl will be calculated using the Cockcroft-Gault formula (Cockcroft-Gault
formula) CrCl (mL/min) = {(140 - age) × weight (kg) × 0.85}/ (serum creatinine.
(mg/dL) × 72) ii .Urine protein < 2+ or 24-hour (h) urine protein quantification <
1.0 g.
c) Liver: i. Serum total bilirubin (TBil) ≤ 1.5 × ULN ii. AST and ALT ≤ 2.5× ULN
iii. Serum albumin (ALB) ≥ 28 g/L d) Coagulation function: i. International
normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
(e.g.
If the subject is receiving anticoagulant therapy, the subject must receive a stable dose
of anticoagulant and have coagulation during screening.
Parameters (PT/INR and APTT) were within the expected range for anticoagulant therapy).
e) Heart function: i. Left ventricular ejection fraction (LVEF) ≥ 50%.
- Female subjects with childbearing potential must undergo a urine or serum pregnancy
test within 3 days before taking the drug for the first time (if the urine pregnancy
test result cannot be confirmed to be negative, a serum pregnancy test must be
performed, and the serum pregnancy result shall prevail). and the result was
negative. If a female subject of childbearing potential has sexual intercourse with
a non-sterilized male partner, the subject must use an acceptable method of
contraception since screening and must agree to continue using contraception methods
for 120 days after the last dose of the study drug. Whether to discontinue
contraception after this time point should be discussed with the investigator.
Cyclic abstinence and safe period contraception are unacceptable methods of
contraception.
1. Women of childbearing potential are those who have not been surgically
sterilized (i.e., bilateral fallopian tube ligation, bilateral oophorectomy, or
total hysterectomy) or who have not undergone menopause (menopause is defined
as at least one without alternative medical reasons). 12 consecutive months of
amenorrhea and serum follicle-stimulating hormone levels within the laboratory
reference range for postmenopausal women);
2. Highly effective contraceptive methods refer to contraceptive methods that have
a very low contraceptive failure rate (e.g. less than 1% per year) when used
correctly and consistently. Not all birth control methods are highly effective.
In addition to barrier contraceptive methods, female subjects of childbearing
potential must also use hormonal contraceptive methods (such as birth control
pills) alone to ensure that pregnancy does not occur.
- Subjects are willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other requirements of the study.
Exclusion Criteria:
- The histopathological types are small cell carcinoma, gastric adenocarcinoma, etc.
- In addition to cervical cancer, subjects suffered from other malignant tumors within
3 years before enrollment. Subjects with other malignant tumors that have been cured
by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial
bladder cancer, breast cancer, etc., are not excluded.
- Enroll in another clinical study at the same time, unless it is an observational,
non-interventional clinical study or the follow-up period of an interventional
study.
- Patients with distant tumor metastasis or local and regional lymph node metastasis.
- Patients who received non-specific immunomodulatory therapy (such as interleukins,
interferons, thymosin, tumor necrosis factor, etc., excluding IL-11 used to treat
thrombocytopenia) within 2 weeks before the first medication; Received non-specific
immunomodulatory therapy within 1 week before the first medication Chinese herbal
medicine or Chinese patent medicine with anti-tumor indications.
- Suffering from active autoimmune diseases that require systemic treatment (such as
disease-modifying drugs, corticosteroids, immunosuppressive treatment), Replacement
therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency) is not considered a systemic therapy.
- Patients have a history of non-infectious pneumonia or pneumonia requiring systemic
glucocorticoid treatment or a current history of interstitial lung disease.
- With a history of severe bleeding tendency or coagulation disorder.
- Patients with currently uncontrolled comorbid diseases, including but not limited to
decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders,
severe active peptic ulcer disease or gastritis, or a mental illness/social
condition that would limit the subject's ability to comply with research
requirements or affect the subject's ability to provide written informed consent.
- Patients with history of myocarditis, cardiomyopathy, and malignant arrhythmia.
Patients suffered unstable angina, congestive heart failure or vascular disease
requiring hospitalization (such as aortic aneurysm or peripheral venous thrombosis
requiring surgical repair) within 12 months before the first dose, or other heart
damages (such as poorly controlled arrhythmia, myocardial infarction or ischemia)
that may affect the safety evaluation of the study.
Patients with a history of esophageal and gastric varices, severe ulcers, unhealed
wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction,
intra-abdominal abscess or acute gastrointestinal bleeding within 6 months before the
first administration; Patients suffered any arterial thromboembolic event, NCI CTCAE
version 5.0 grade 3 or above, venous thromboembolism, transient ischemic attack,
cerebrovascular accident, hypertensive crisis or hypertensive encephalopathy within 6
months before the first dose; Patients with acute exacerbation of COPD within 1 month
before first dose; Current hypertension with systolic blood pressure ≥160mmHg or
diastolic blood pressure ≥100mmHg after treatment with oral antihypertensive drugs.
- Patients with active or clear history of inflammatory bowel disease (such as Crohn's
disease, ulcerative colitis or chronic diarrhea).
- Patients with serious infection occurring within 4 weeks before the first dose,
including but not limited to complications requiring hospitalization, sepsis or
severe pneumonia; Patients with active infection (excluding antiviral therapy for
hepatitis B or hepatitis C) that has been treated with systemic anti-infectious
therapy within 10 days before the first dose.
- Patients suffered major surgery or serious trauma within 30 days before the first
medication; or minor local surgery within 3 days before the first medication
(excluding central venous catheterization via peripheral venipuncture).
- Patients with a history of immunodeficiency; those with positive HIV antibody test;
Patients who are taking long-term systemic corticosteroids or other
immunosuppressants.
- Subjects who are known to have active pulmonary tuberculosis (TB) and are suspected
of having active TB need to undergo clinical examination to exclude (such as sputum
tuberculosis bacilli examination, chest X-ray, etc.); known active syphilis
infection.
- Patients with history of allogeneic organ transplantation and allogeneic
hematopoietic stem cell transplantation.
- Subjects with untreated active hepatitis B (HBsAg positive and HBV-DNA exceeding
1000 copies/ml (200 IU/ml) or higher than the lower limit of detection).Subjects
with hepatitis B are required to receive anti-hepatitis B virus treatment during the
study treatment period; subjects with active hepatitis C (HCV antibody positive and
HCV-RNA levels above the lower limit of detection).
- Patients who have received a live vaccine within 30 days before the first dose, or
plan to receive a live vaccine during the study.
- Patients who are hypersensitive to any component of any study drug; with history of
severe hypersensitivity reactions to other monoclonal antibodies.
- Patients with history of mental illness, substance abuse, alcoholism, or drug abuse.
- Pregnant or lactating women.
- Patients with any past or current disease, treatment, or laboratory test abnormality
may confuse the research results and affect the subject's full participation in the
research, or participation in the research may not be in the best interests of the
subject.
Gender:
Female
Minimum age:
18 Years
Maximum age:
45 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Jin Li
Phone:
fudanlijin@163.com
Email:
fudanlijin@163.com
Start date:
September 1, 2023
Completion date:
December 30, 2028
Lead sponsor:
Agency:
Xiaohua Wu
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06209294
