Phase II Study on Neoadjuvant Therapy of AK104 Combined With Nab-paclitaxel/Carboplatin in Fertility Preserving Surgery

NCT06209294 | Recruiting Phase 2 DMC

• 1 other identifier: NACI-CC-FSS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neoadjuvant Immunotherapy; Cervical Cancer; Fertility-sparing Surgery

Outcome Measures

Primary Outcomes (4)

• Adverse Events (AEs)

  To evaluate the safety of AK104 combined with nab-paclitaxel and carboplatin in the neoadjuvant treatment of cervical cancer

  Up to approximately 6 mouths

• Tumor regression rate

  The change of tumor size after the treatment,

  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.

  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.

  Up to approximately 6 mouths

Secondary Outcomes (5)

• Major pathological response (MPR) rate

  within 14 working days after operation

• Pathological Complete Response (pCR) rate

  within 14 working days after operation

• Progression-free survival

  Nearly 5 years after treatment

• Overall survival

  Nearly 5 years after treatment

• Pregnant rates

  Nearly 5 years after treatment

Other Outcomes (1)

• Ratio of different immune cells in tumor micro-environment after neoadjuvant treatment

  Up to approximately 6 mouths

Study Arms (1)

Experimental: AK104 combined with nab-paclitaxel and carboplatin

EXPERIMENTAL

Carboplatin, nab-paclitaxel and AK104 as neoadjuvant treatment before fertility-sparing surgery

Drug: AK104; Drug: Carboplatin; Drug: Nab paclitaxel

Interventions

AK104 DRUG

AK104(10 mg/kg) d1,22

Experimental: AK104 combined with nab-paclitaxel and carboplatin

Carboplatin DRUG

AUC=2 d1,8,15,22, 29, 36

Experimental: AK104 combined with nab-paclitaxel and carboplatin

Nab paclitaxel DRUG

125mg／m2 d1,8,15,22,29,36

Experimental: AK104 combined with nab-paclitaxel and carboplatin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xiaohua Wu: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Carboplatin; Taxes

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations

Central Study Contacts

Jin Li

CONTACT

fudanlijin@163.com; fudanlijin@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 17, 2024
• Study Start: September 1, 2023
• Primary Completion: December 30, 2025
• Study Completion (Estimated): December 30, 2028
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)