Neoadjuvant ImmunotherapyPhase 2NCT06209294
Phase II Study on Neoadjuvant Therapy of AK104 Combined With Nab-paclitaxel/Carboplatin in Fertility Preserving Surgery
A Phase 2 study testing AK104, Carboplatin and Nab paclitaxel in people with Neoadjuvant Immunotherapy and Cervical Cancer, run by Xiaohua Wu at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Neoadjuvant Immunotherapy, Cervical Cancer, Fertility-sparing Surgery
- What is being tested?
- AK104, Carboplatin and Nab paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2023to 30 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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:
- 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.
- 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).
- 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.
- 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);
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality
Jin Li, fudanlijin@163.com, fudanlijin@163.com
About this study
Official title: Phase II Study on Neoadjuvant Therapy of AK104 Combined With Nab-paclitaxel/Carboplatin in Fertility Preserving Surgery for Stage IB2-IB3 Cervical Cancer (FIGO 2018)
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.
- Being tested
- AK104, Carboplatin, Nab paclitaxel
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK104Drug
AK104(10 mg/kg) d1,22
CarboplatinDrug
AUC=2 d1,8,15,22, 29, 36
Nab paclitaxelDrug
125mg/m2 d1,8,15,22,29,36
| Study group | Role | What they receive |
|---|---|---|
| Experimental: AK104 combined with nab-paclitaxel and carboplatin | Experimental | Carboplatin, nab-paclitaxel and AK104 as neoadjuvant treatment before fertility-sparing surgery Receives: Drug: AK104; Drug: Carboplatin; Drug: Nab paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs)
To evaluate the safety of AK104 combined with nab-paclitaxel and carboplatin in the neoadjuvant treatment of cervical cancer
Measured: Up to approximately 6 mouths
Tumor regression rate
The change of tumor size after the treatment,
Measured: within 14 working days after operation
Objective response rate
Objective response rate is the proportion of subjects with complete response(CR) or partial response(PR) , based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Measured: 4-6 weeks after the second cycle(21 days per cycle) of neoadjuvant treatment
The success rate of fertility sparing surgery
The rates of patients who can successfully preserve fertility.
Measured: Up to approximately 6 mouths
Secondary outcomes (5)
Major pathological response (MPR) rate
MPR rate is defined as the percentage of participants having ≤ 10% viable tumor cells in the pathological examination of resected specimens.
Measured: within 14 working days after operation
Pathological Complete Response (pCR) rate
pCR rate is defined as the percentage of participants lacking of evidence of viable tumor cells in the pathological examination of resected specimens.
Measured: within 14 working days after operation
Progression-free survival
Survival of patients
Measured: Nearly 5 years after treatment
Overall survival
Overall survival of patients
Measured: Nearly 5 years after treatment
Pregnant rates
Pregnant rates of patients after treatment
Measured: Nearly 5 years after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start1 Sep 2023
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoadjuvant ImmunotherapyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiaohua Wu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xiaohua Wu, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06209294
- Sponsor's protocol ID
- NACI-CC-FSS
- Status last verified
- Jan 2024
- First submitted
- 20 Dec 2023
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data is available per require after approved by ethics broad
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study on Neoadjuvant Therapy of AK104 Combined With Nab-paclitaxel/Carboplatin in Fertility Preserving Surgery for Stage IB2-IB3 Cervical Cancer (FIGO 2018)
- ClinicalTrials.gov ID
- NCT06209294
- Acronym / sponsor ID
- NACI-CC-FSS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Xiaohua WuUniversity, hospital or other
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: AK104 combined with nab-paclitaxel and carboplatin | Experimental | Drug: AK104, Drug: Carboplatin, Drug: Nab paclitaxelCarboplatin, nab-paclitaxel and AK104 as neoadjuvant treatment before fertility-sparing surgery |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AK104AK104(10 mg/kg) d1,22 | Drug | Experimental: AK104 combined with nab-paclitaxel and carboplatin |
| CarboplatinAUC=2 d1,8,15,22, 29, 36 | Drug | Experimental: AK104 combined with nab-paclitaxel and carboplatin |
| Nab paclitaxel125mg/m2 d1,8,15,22,29,36 | Drug | Experimental: AK104 combined with nab-paclitaxel and carboplatin |
Primary outcome
Adverse Events (AEs)
Time frame: Up to approximately 6 mouths
To evaluate the safety of AK104 combined with nab-paclitaxel and carboplatin in the neoadjuvant treatment of cervical cancer
Tumor regression rate
Time frame: within 14 working days after operation
The change of tumor size after the treatment,
Objective response rate
Time frame: 4-6 weeks after the second cycle(21 days per cycle) of neoadjuvant treatment
Objective response rate is the proportion of subjects with complete response(CR) or partial response(PR) , based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
The success rate of fertility sparing surgery
Time frame: Up to approximately 6 mouths
The rates of patients who can successfully preserve fertility.
5 secondary outcomes
Major pathological response (MPR) rate
Time frame: within 14 working days after operation
Pathological Complete Response (pCR) rate
Time frame: within 14 working days after operation
Progression-free survival
Time frame: Nearly 5 years after treatment
Overall survival
Time frame: Nearly 5 years after treatment
Pregnant rates
Time frame: Nearly 5 years after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Individual participant dataSharing planned: No. Data is available per require after approved by ethics broad
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AK104, Carboplatin and Nab paclitaxel in people with Neoadjuvant Immunotherapy and Cervical Cancer, run by Xiaohua Wu at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jin Li (fudanlijin@163.com, fudanlijin@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AEs) (time frame: Up to approximately 6 mouths). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2024.