Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)
- Conditions
- Locally Advanced Cervical Cancer
- Interventions
- Other: Placebo
- Registration Number
- NCT06079671
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 800
For inclusion in the study, patients should fulfill the following criteria:
- Female.
- Aged at least 15 years at the time of screening.
- Body weight > 35 kg.
- Histologically documented FIGO 2018 Stage IIIA to IVA cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, with no evidence of metastatic disease.
- Initial staging procedures performed no more than 42 days prior to the first dose of CCRT.
- Provision of FFPE tumor sample to assess the PD-L1 expression.
- Must not have progressed following CCRT, participants with persistent disease after definitive CCRT must not be amenable to other available therapies with curative intent.
- WHO/ECOG performance status of 0 or 1.
- Adequate organ and bone marrow function.
- Capable of providing signed informed consent.
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
- Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer.
- Evidence of metastatic disease.
- Intent to administer a fertility-sparing treatment regimen.
- History of organ transplant or allogenic stem cell transplant.
- Active or prior documented autoimmune or inflammatory disorders.
- Uncontrolled intercurrent illness.
- History of another primary malignancy except for a) Malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease.
- Unresolved toxicities from previous CCRT except for irreversible toxicity that is not reasonably expected to be exacerbated.
- Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula.
- History of anaphylaxis to any biologic therapy or vaccine.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of the study intervention is excluded. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication or chemotherapy premedication) or a single dose for palliative purpose (eg, pain control).
- Patients who have undergone a previous hysterectomy, including a supracervical hysterectomy, or will have a hysterectomy as part of their initial cervical cancer therapy.
- Any prior (besides prior CCRT) or concurrent treatment for cervical cancer.
- Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
- Exposure to immune mediated therapy prior to the study for any indication.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
- Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo Volrustomig Volrustomig Volrustomig
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) based on the investigator assessment in all randomized participants (FAS) The study duration will be approximately 40 months. 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 Outcome Measures
Name Time Method Overall Survival (OS) in all randomized participants. Regarding the demonstration OS in participants, the study duration will be approximately 6 years. OS defined as time from randomization until the date of death due to any cause.
Objective Response Rate (ORR) in all randomized participants. The study duration will be approximately 40 months. 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. The study duration will be approximately 40 months. 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. The study duration will be approximately 40 months. 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. The study duration will be approximately 40 months. 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. The study duration will be approximately 40 months. 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. The study duration will be approximately 40 months. Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence.
PK of Volrustomig The study duration will be approximately 40 months. Concentration of Volrustomig in serum and PK parameters as data allow.
The immunogenicity of volrustomig The study duration will be approximately 40 months. Incidence of ADAs against volrustomig in serum.
Incidence of adverse events of Volrustomig compared to placebo. The study duration will be approximately 40 months. 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.
Participant-reported disease-related symptoms The study duration will be approximately 40 months. 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.
Participant-reported physical functioning The study duration will be approximately 40 months. 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. The study duration will be approximately 40 months. 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.
Trial Locations
- Locations (1)
Research Site
🇹🇷Karsiyaka, Turkey