Clinical trial NCT06079671: Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)
Official title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-centre, Global Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer Who Have Not Progressed Following Platinum-based, Concurrent Chemoradiation Therapy (eVOLVE-Cervical)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Locally Advanced Cervical Cancer
Keywords: Locally Advanced Cervical Cancer;
Adolescent and Young Adult;
Volrustomig
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Gynecologic Oncology Group Foundation
name: European Network for Gynaecological Oncological Trial Groups
First posted: 2023-10-12
Enrollment: 800
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.
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 42 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.
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 exclusion criteria are fulfilled:

1. Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer.
2. Evidence of metastatic disease.
3. Intent to administer a fertility-sparing treatment regimen.
4. History of organ transplant or allogenic stem cell transplant.
5. Active or prior documented autoimmune or inflammatory disorders.
6. Uncontrolled intercurrent illness.
7. 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.
8. Unresolved toxicities from previous CCRT except for irreversible toxicity that is not reasonably expected to be exacerbated.
9. Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula.
10. History of anaphylaxis to any biologic therapy or vaccine.
11. 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).
12. Patients who have undergone a previous hysterectomy, including a supracervical hysterectomy, or will have a hysterectomy as part of their initial cervical cancer therapy.
13. Any prior (besides prior CCRT) or concurrent treatment for cervical cancer.
14. Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
15. Exposure to immune mediated therapy prior to the study for any indication.
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
17. Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention.

Primary outcomes:
measure: Progression-free Survival (PFS) based on the investigator assessment in all randomized participants (FAS)
timeFrame: The study duration will be approximately 40 months.
Secondary outcomes:
measure: Overall Survival (OS) in all randomized participants.
timeFrame: Regarding the demonstration OS in participants, the study duration will be approximately 6 years.
measure: Objective Response Rate (ORR) in all randomized participants.
timeFrame: The study duration will be approximately 40 months.
measure: Duration of Response (DoR) in all randomized participants.
timeFrame: The study duration will be approximately 40 months.
measure: Time to First Subsequent Therapy or death (TFST) in all randomized participants.
timeFrame: The study duration will be approximately 40 months.
measure: Time to second progression or death (PFS2) in all randomized participants.
timeFrame: The study duration will be approximately 40 months.
measure: PFS by BICR in all randomized participants.
timeFrame: The study duration will be approximately 40 months.
measure: The incidence of local progression, and distant disease progression as the first documented progression event in all randomized participants.
timeFrame: The study duration will be approximately 40 months.
measure: PK of Volrustomig
timeFrame: The study duration will be approximately 40 months.
measure: The immunogenicity of volrustomig
timeFrame: The study duration will be approximately 40 months.
measure: Incidence of adverse events of Volrustomig compared to placebo.
timeFrame: The study duration will be approximately 40 months.
measure: Participant-reported disease-related symptoms
timeFrame: The study duration will be approximately 40 months.
measure: Participant-reported physical functioning
timeFrame: The study duration will be approximately 40 months.
measure: Participant-reported global health status/Quality of Life.
timeFrame: The study duration will be approximately 40 months.
Other outcomes:
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country: Taiwan
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country: Turkey
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city: Ankara
country: Turkey
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city: Ankara
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city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
Study officials:
References: