Induction Chemotherapy Combined With Immunotherapy Followed by Concurrent Chemoradiation in Advanced Cervical Cancer

University of Electronic Science and Technology of China (UESTC)

Status and phase: Enrolling; Phase 3

Conditions: Cervical Cancer

Treatments: Radiation: CCRT; Radiation: Brachytherapy; Drug: Neoadjuvant Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05173272

KY-2021-109

Details and patient eligibility

About

The main objective of this study is to determine whether neoadjuvant chemotherapy combined with slulimumab sequential concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced cervical cancer could improve progression-free survival rates.

Women in the experimental arm will receive neoadjuvant chemotherapy (cisplatin plus paclitaxel) combined with slulimumab every 21 days during 2 cycles followed by concurrent chemoradiation therapy. Women in the control arm will receive concurrent chemoradiation therapy alone.

286 patients will be recruited during 2 years, with 3 years of follow up period.

Enrollment: 286 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years old
• Patients must have histologically confirmed cervical cancer with adenocarcinoma, adenosquamous or squamous histology and FIGO 2018 Ib3-IIIc2.
• According to the RECIST 1.1 standard, the subject must have at least one measurable target lesion
• No prior treatment
• Expected survival period ≥ 3 months
• ECOG score: 0-1
• No obvious signs of hematological diseases, ANC≥1.5×10^9/L, platelet count≥100×10^9/L, Hb≥90g/L, WBC≥3.0×10^9/L, and no bleeding tendency before enrollment;
• Adequate hepato-renal function is needed, including: Total bilirubin (TBIL)≤1.5×ULN (Gilbert syndrome allows ≤5×ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN Serum creatinine (Cr) ≤ 1.5 × ULN or endogenous creatinine clearance ≥ 50mL/min
• Cardiac Function: left ventricular ejection fraction (LVEF) >=50%;
• Patients voluntarily participated in the study and signed informed consent

Exclusion criteria

• Pregnant or breastfeeding female patients (women of child-bearing potential must confirm that the pregnancy test is negative within 7 days before the first administration. If it is positive, ultrasound examination must be performed to exclude pregnancy), or women of child-bearing potential who refused to receive contraceptive measures
• Combined with other malignant tumors, except for cured skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of any other part
• Existence of any bone marrow dysplasia and other abnormal hematopoietic diseases
• Active infections, HIV infections, and viral hepatitis that require systematic treatment
• Patients with≥Grade 1 peripheral neuropathy according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 5.0
• Had severe cardiovascular diseases such as cerebrovascular accident, myocardial infarction, hypertension that cannot be controlled after drug intervention, unstable angina pectoris, heart failure (NYHA 2-4) and arrhythmia that need drug intervention within 6 months
• It is known to have a history of allergies to research drugs or drug components
• Has clinically significant thyroid dysfunction before enrollment;
• Has participated in other anti-tumor intervention clinical trials within 30 days before the first medication
• Have a clear history of dementia, mental state changes or any mental illness that will hinder understanding or informed consent
• The investigator believes that the patient is not suitable for participating in this clinical research

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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286 participants in 2 patient groups

Experimental: Neoadjuvant Therapy+CCRT

Experimental group

Description:

Patients will be treated with 2 cycles of neoadjuvant chemotherapy (Cisplatin 50 mg/m\^2 d1 q21+ Paclitaxel 175 mg/m\^2 d1 q21) combined with serplulimab （300mg d1 q21）. After that, weekly cisplatin 30mg/m\^2 for 4 or 5 weeks is administered concomitant with external beam radiotherapy (45-50.4Gy) in 1.8-2 daily fractions and a 10-20 Gy boost to reach a total dose of 65 Gy when there was unresectable lymph nodes. The primary cervical tumor is the boosted, using image guided 3D brachytherapy or 2D brachytherapy, with an additional 30-40 Gy to HRCTV (3D brachytherapy) or to point A (2D brachytherapy), to achieve a total dose of 80 Gy for small-volume cervical tumors or 85 Gy for larger-volume cervical tumors. All radiotherapy should be completed within eight weeks.

Treatment:

Radiation: CCRT

Drug: Neoadjuvant Therapy

Radiation: Brachytherapy

Experimental: CCRT alone

Experimental group

Description:

weekly cisplatin 40mg/m\^2 for 4 or 5 weeks is administered concomitant with external beam radiotherapy (45-50.4Gy) in 1.8-2 daily fractions and a 10-20 Gy boost to reach a total dose of 65 Gy when there was unresectable lymph nodes. The primary cervical tumor is the boosted, using image guided 3D brachytherapy or 2D brachytherapy, with an additional 30-40 Gy to HRCTV (3D brachytherapy) or to point A (2D brachytherapy), to achieve a total dose of 80 Gy for small-volume cervical tumors or 85 Gy for larger-volume cervical tumors. All radiotherapy should be completed within eight weeks.

Treatment:

Radiation: CCRT

Radiation: Brachytherapy