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Study Of Candonilimab Combined With Radiotherapy In The Treatment of Locally Advanced Cervical Cancer

Primary Purpose

Locally Advanced Cervical Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Candonilimab(AK104)
EBRT
BT
Sponsored by
Chongqing University Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Cervical Cancer focused on measuring Cervical Cancer, Local advanced, Concurrent chemoradiotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Able to understand and voluntarily sign written informed consent. Women aged ≥18 years at the time of study entry. Eastern Cancer Cooperative performance status (ECOG PS) score of 0 or 1. Life expectancy ≥12 weeks. Participants' intolerance to chemotherapy regimens. Histologically confirmed cervical cancer. Histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix; Not receiving systemic anti-tumour therapy (including but not limited to radiotherapy, targeted therapy and immunotherapy, etc; concurrent chemotherapy is not included. Note: Removal or biopsy of pelvic lymph nodes or para-aortic lymph nodes for the purpose of clinical staging is allowed). Locally advanced cervical cancer(LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2018 Stage IB3/IIA2, IIB-IVA. At least one measurable tumor lesion according to RECIST v1.1 criteria. Available archived tumor tissue samples or recent biopsies. Adequate organ function. For fertile women with negative serum pregnancy and effective contraception within 7 days before administration (until 120 days after the last administration of the study drug and at least 180 days after radiotherapy) Exclusion Criteria: Other histological types of cervical cancer (eg, neuroendocrine carcinoma, small cell carcinoma, sarcoma, etc). Evidence of distant metastases. Have received total hysterectomy. Subject with other active malignancies within 2 years prior to randomization. Subject who cannot receive brachytherapy. Active or prior documented autoimmune disease that may relapse. History of interstitial lung disease or noninfectious pneumonitis. Subject with the clinically significant cardio-cerebrovascular disease. History of severe hypersensitivity reactions to other mAbs. Prior allogeneic stem cell transplantation or organ transplantation. Subjects who require systemic treatment with glucocorticoid (>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to randomization. Receipt of live attenuated vaccines within 30 days prior to the first dose of the study drug. Prior exposure to any experimental antitumor vaccines, or any agent targeting T-cell costimulation or immune checkpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137 or anti-OX40 antibody, etc). Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drug or interpretation of subject safety or study results.

Sites / Locations

  • Chongqing university Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment arm

Arm Description

Participants receive candonilimab at a dose of 10 mg/kg, Q3W (Day 1 of each 21 day treatment cycle) via IV infusion, until disease progression, intolerable toxicity, investigator determines that the participant cannot continue to benefit, withdraws informed consent, or candonilimab treatment over 2 years. During the q3w dosing period of candonilimab, participants receive radiotherapy including external beam radiotherapy (EBRT) and followed by brachytherapy.

Outcomes

Primary Outcome Measures

ORR assessed by Investigator
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR per RECIST v1.1.

Secondary Outcome Measures

DCR
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
PFS
Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
OS
OS is the time from randomization to death due to any cause
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score and Physical Function Score.
The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The change from baseline in EORTC QLQ-C30 score will be presented.
Number of participants with adverse events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Full Information

First Posted
December 24, 2022
Last Updated
January 15, 2023
Sponsor
Chongqing University Cancer Hospital
Collaborators
Akeso Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05687851
Brief Title
Study Of Candonilimab Combined With Radiotherapy In The Treatment of Locally Advanced Cervical Cancer
Official Title
A Single-arm, Multicenter, Phase II Study to Evaluate Candonilimab(AK104) Combined With Radiotherapy For The Treatment of Locally Advanced Cervical Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 29, 2022 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chongqing University Cancer Hospital
Collaborators
Akeso Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Candonilimab(AK104)is a humanized IgG1 bispecific antibody that targets PD-1 and CTLA-4. This is a single-arm, multicenter, open-label, phase II study, the purpose of this study is to evaluate the efficacy and safety of candonilimab plus radiotherapy in participants with locally advanced cervical cancer who do not tolerate chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Cervical Cancer
Keywords
Cervical Cancer, Local advanced, Concurrent chemoradiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
treatment arm
Arm Type
Experimental
Arm Description
Participants receive candonilimab at a dose of 10 mg/kg, Q3W (Day 1 of each 21 day treatment cycle) via IV infusion, until disease progression, intolerable toxicity, investigator determines that the participant cannot continue to benefit, withdraws informed consent, or candonilimab treatment over 2 years. During the q3w dosing period of candonilimab, participants receive radiotherapy including external beam radiotherapy (EBRT) and followed by brachytherapy.
Intervention Type
Drug
Intervention Name(s)
Candonilimab(AK104)
Intervention Description
q3w iv
Intervention Type
Radiation
Intervention Name(s)
EBRT
Intervention Description
45-50.4Gy
Intervention Type
Radiation
Intervention Name(s)
BT
Intervention Description
≥80Gy
Primary Outcome Measure Information:
Title
ORR assessed by Investigator
Description
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR per RECIST v1.1.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
DCR
Description
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Time Frame
Up to 2 years
Title
PFS
Description
Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time Frame
Up to approximately 30 months
Title
OS
Description
OS is the time from randomization to death due to any cause
Time Frame
Up to approximately 40 months
Title
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score and Physical Function Score.
Description
The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The change from baseline in EORTC QLQ-C30 score will be presented.
Time Frame
Baseline and up to approximately 40 months
Title
Number of participants with adverse events (AEs)
Description
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame
Up to approximately 40 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to understand and voluntarily sign written informed consent. Women aged ≥18 years at the time of study entry. Eastern Cancer Cooperative performance status (ECOG PS) score of 0 or 1. Life expectancy ≥12 weeks. Participants' intolerance to chemotherapy regimens. Histologically confirmed cervical cancer. Histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix; Not receiving systemic anti-tumour therapy (including but not limited to radiotherapy, targeted therapy and immunotherapy, etc; concurrent chemotherapy is not included. Note: Removal or biopsy of pelvic lymph nodes or para-aortic lymph nodes for the purpose of clinical staging is allowed). Locally advanced cervical cancer(LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2018 Stage IB3/IIA2, IIB-IVA. At least one measurable tumor lesion according to RECIST v1.1 criteria. Available archived tumor tissue samples or recent biopsies. Adequate organ function. For fertile women with negative serum pregnancy and effective contraception within 7 days before administration (until 120 days after the last administration of the study drug and at least 180 days after radiotherapy) Exclusion Criteria: Other histological types of cervical cancer (eg, neuroendocrine carcinoma, small cell carcinoma, sarcoma, etc). Evidence of distant metastases. Have received total hysterectomy. Subject with other active malignancies within 2 years prior to randomization. Subject who cannot receive brachytherapy. Active or prior documented autoimmune disease that may relapse. History of interstitial lung disease or noninfectious pneumonitis. Subject with the clinically significant cardio-cerebrovascular disease. History of severe hypersensitivity reactions to other mAbs. Prior allogeneic stem cell transplantation or organ transplantation. Subjects who require systemic treatment with glucocorticoid (>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to randomization. Receipt of live attenuated vaccines within 30 days prior to the first dose of the study drug. Prior exposure to any experimental antitumor vaccines, or any agent targeting T-cell costimulation or immune checkpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137 or anti-OX40 antibody, etc). Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drug or interpretation of subject safety or study results.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xingtao Long, MD
Phone
+8602365075619
Email
longxingtao2009@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qi Zhou, MD
Organizational Affiliation
Chongqing University Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chongqing university Cancer Hospital
City
Chongqing
State/Province
CHN
ZIP/Postal Code
400000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xingtao Long, MD
Phone
+86232365075619
Email
longxingtao2009@163.com
First Name & Middle Initial & Last Name & Degree
Qi Zhou, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study Of Candonilimab Combined With Radiotherapy In The Treatment of Locally Advanced Cervical Cancer

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