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

NCT05173272 | Recruiting Phase 3

• 1 other identifier: KY-2021-109
• Study Type: interventional
• Target: 286
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of suspected disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD.

  Up to approximately 36 months

Secondary Outcomes (3)

• Overall Survival (OS)

  Up to approximately 48 months

• Objective Response Rate (ORR)

  Up to approximately 36 months

• Number of Participants Who Experience One or More Adverse Events (AEs)

  Up to approximately 36 months

Study Arms (2)

Experimental: Neoadjuvant Therapy+CCRT

EXPERIMENTAL

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.

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

Experimental: CCRT alone

EXPERIMENTAL

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.

Radiation: CCRT; Radiation: Brachytherapy

Interventions

Neoadjuvant Therapy DRUG

Cisplatin 50 mg/m\^2 d1 q21+ Paclitaxel 175 mg/m\^2 d1 q21+serplulimab 300mg d1 q21

Also known as: Neoadjuvant chemotherapy combined with Serplulimab

Experimental: Neoadjuvant Therapy+CCRT

CCRT RADIATION

weekly cisplatin for 4 or 5 weeks is administered concomitant with EBRT (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.

Also known as: chemoradiation

Experimental: CCRT alone; Experimental: Neoadjuvant Therapy+CCRT

Brachytherapy RADIATION

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.

Experimental: CCRT alone; Experimental: Neoadjuvant Therapy+CCRT

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sichuan Cancer Hospital and Research Institute: lead

Study Sites (1)

Sicchuan cancer hospital

Chengdu, Sichuan, 610000, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Neoadjuvant Therapy; Chemoradiotherapy; Brachytherapy

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)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Guonan Zhang

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guonan Zhang

CONTACT

86-13881866599; zhanggn@hotmail.com

Hong Liu

CONTACT

86-13693447854; liuhaotian12@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Gynecologic Oncology Center, Clinical Professor

Study Record Dates

• First Submitted: December 26, 2021
• First Posted: December 29, 2021
• Study Start: July 24, 2023
• Primary Completion (Estimated): December 28, 2027
• Study Completion (Estimated): December 28, 2028
• Last Updated: December 27, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)