Locally Advanced Cervical Cancer
Conditions
Keywords
Locally Advanced Cervical Cancer;, Adolescent and Young Adult;, Volrustomig
Brief summary
This is a phase III, randomized, double-blind, placebo-controlled, multi-center, global study to explore the efficacy and safety of volrustomig in women with high-risk LACC (FIGO 2018 stage IIIA to IVA cervical cancer) who have not progressed following platinum-based CCRT.
Detailed description
Women with locally advanced cervical cancer will be randomized in a 1:1 ratio to receive treatment with Volrustomig or Placebo.
Interventions
BIOLOGICALVolrustomig
IV Infusion
OTHERPlacebo
IV Infusion
Sponsors
AstraZeneca
Gynecologic Oncology Group Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For inclusion in the study, patients should fulfill the following criteria: 1. Female. 2. Aged at least 15 years at the time of screening. Note: Participants \< 18 years of age: physical changes should be aligned with Tanner Stage III. 3. Body weight \> 35 kg. 4. Histologically documented FIGO 2018 Stage IIIA to IVA cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, with no evidence of metastatic disease. 5. Initial staging procedures performed no more than 56 days prior to the first dose of CCRT. 6. Provision of FFPE tumor sample to assess the PD-L1 expression. 7. Must not have progressed following CCRT, participants with persistent disease after definitive CCRT must not be amenable to other available therapies with curative intent. 8. WHO/ECOG performance status of 0 or 1; duration of life expectancy of ≥ 12 weeks. 9. Adequate organ and bone marrow function. 10. Capable of providing signed informed consent.
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) based on the investigator assessment in all randomized participants (FAS) | Up to approximately 7 years | PFS is defined as the time from date of randomization until RECIST 1.1- defined radiological progression or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participant-reported physical functioning | Up to approximately 7 years | Change from baseline of physical functioning as measured by the Patient Reported Outcomes Measurement Information System - Short Form - Physical Functioning 8c (PROMIS SF-PF 8c). The score of scale for PROMIS SF-PF 8c is from 1-5. |
| Participant-reported global health status/Quality of Life | Up to approximately 7 years | Change from baseline of Global Health Status/ Quality of Life (GHS/QoL) as measured by the European Organization for Research and Treatment of Cancer IL172 (EORTC IL172). The score of scale for EORTC IL172 is from 1-7. |
| Overall Survival (OS) in all randomized participants | Up to approximately 7 years | OS defined as time from randomization until the date of death due to any cause. |
| Objective Response Rate (ORR) in all randomized participants | Up to approximately 7 years | ORR is defined as the proportion of participants who have a CR or PR, as determined by Investigator per RECIST 1.1 |
| Duration of Response (DoR) in all randomized participants | Up to approximately 7 years | DoR in participants with a CR or PR: Time from date of first detection of CR or PR until the date of RECIST 1.1-defined radiological progression or histopathologically confirmed progression. |
| Time to First Subsequent Therapy or death (TFST) in all randomized participants | Up to approximately 7 years | TFST: The time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause. |
| Time to second progression or death (PFS2) in all randomized participants | Up to approximately 7 years | PFS2: The time from randomization to the earliest of the progression event (following the initial Investigator-assessed progression), after first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice. |
| PFS by BICR in all randomized participants | Up to approximately 7 years | Endpoints based on the PFS by BICR assessment according to RECIST 1.1. |
| The incidence of local progression, and distant disease progression as the first documented progression event in all randomized participants | Up to approximately 7 years | Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence. |
| PK of volrustomig | Up to approximately 7 years | Concentration of volrustomig in serum and PK parameters as data allow. |
| The immunogenicity of volrustomig | Up to approximately 7 years | Incidence of ADAs against volrustomig in serum. |
| Participant-reported disease-related symptoms | Up to approximately 7 years | Change from baseline as measured by the European Organization for Research and Treatment of Cancer IL318 (EORTC IL318, Symptom Experience subscale of the EORTC Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24)). The score of scale for EORTC IL318 is from 1-4. |
| Incidence of adverse events of volrustomig compared to placebo | Up to approximately 7 years | An AE is defined as the development of any untoward medical occurrence (other than progression of the malignancy under evaluation) in a patient or clinical study participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. |
Countries
Brazil, Canada, China, Denmark, Germany, India, Italy, Japan, Mexico, Norway, Peru, Poland, Puerto Rico, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed