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eVOLVECervical: Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT06079671
Collaborator
Gynecologic Oncology Group Foundation (Other), European Network for Gynaecological Oncological Trial Groups (Other)
1,000
Enrollment
86
Locations
2
Arms
73.1
Anticipated Duration (Months)
11.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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 IIIC to IVA cervical cancer with lymph node involvement) who have not progressed following platinum-based CCRT.

Condition or Disease Intervention/Treatment Phase
  • Biological: Volrustomig
  • Other: Placebo
 Phase 3

Detailed Description

Women with locally advanced cervical cancer will be randomized in a 1:1 ratio to receive treatment with Volrustomig or Placebo.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1000 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Sep 22, 2023
Anticipated Primary Completion Date :
Feb 19, 2027
Anticipated Study Completion Date :
Oct 24, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Volrustomig

Volrustomig

Biological: Volrustomig
IV Infusion
Placebo Comparator: Placebo

Placebo

Other: Placebo
IV Infusion
Other Names:
  • Saline

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) in participants with PD-L1 expression based on the investigator assessment [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

    1. Progression-free Survival (PFS) in participants regardless of PD-L1 expression based on the investigator assessment [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.

    2. Overall Survival (OS) in participants regardless of PD-L1 expression. [The study duration will be approximately 6 years.]

      OS defined as time from randomization until the date of death due to any cause.

    3. Overall Survival (OS) in participants with PD-L1 expression [The study duration will be approximately 6 years.]

      OS defined as time from randomization until the date of death due to any cause.

    4. Objective Response Rate (ORR) in participants with PD-L1 expression/regardless of PD-L1 expression. [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

    5. Duration of Response (DoR) in participants with a CR or PR in the PD-L1 expression analysis set/FAS. [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.

    6. Time to First Subsequent Therapy or death (TFST) in the PD-L1 expression analysis set/FAS [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.

    7. Time to second progression or death (PFS2) in the PD-L1 expression analysis set/FAS. [The study duration will be approximately 6 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.

    8. PFS by BICR in the PD-L1 expression analysis set/FAS. [The study duration will be approximately 40 months]

      Endpoints based on the PFS by BICR assessment according to RECIST 1.1.

    9. The incidence of local progression, and distant disease progression as the first documented progression event in the PD-L1 expression analysis set/FAS. [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.

    10. PK of Volrustomig [The study duration will be approximately 40 months.]

      Concentration of Volrustomig in serum.

    11. The immunogenicity of volrustomig. [The study duration will be approximately 40 months]

      Incidence of ADAs against volrustomig in serum.

    12. Incidence of adverse events of Volrustomig compared to placebo; [The study duration will be approximately 40 months.]

      An AE is definded 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.

    13. 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.

    14. 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.

    15. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts 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.

    3. Body weight > 35 kg.

    4. Histologically documented FIGO 2018 Stage IIIC to IVA cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, with lymph node involvement.

    5. Initial staging procedures performed no more than 42 days prior to the first dose of CCRT.

    6. Provision of 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.

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Savannah Georgia United States 31405
    2 Research Site Shreveport Louisiana United States 71103
    3 Research Site Curitiba Brazil 80730-150
    4 Research Site Sao Paulo Brazil 1323001
    5 Research Site São Paulo Brazil 01246-000
    6 Research Site London Ontario Canada N6A 5W9
    7 Research Site Toronto Ontario Canada M4N 3M5
    8 Research Site Montreal Quebec Canada H2X 0C1
    9 Research Site Montreal Quebec Canada H3G 1A4
    10 Research Site Beijing China 100730
    11 Research Site Changde China 415003
    12 Research Site Changsha China 410008
    13 Research Site Changsha China 410013
    14 Research Site Chengdu China 610041
    15 Research Site Chongqing China 400030
    16 Research Site Fuzhou China 350014
    17 Research Site Guangzhou China 510060
    18 Research Site Guangzhou China 510120
    19 Research Site Hangzhou China 310022
    20 Research Site Harbin China 150081
    21 Research Site Kunming China 650118
    22 Research Site Lanzhou China 730000
    23 Research Site Lanzhou China 730050
    24 Research Site Luzhou China 646000
    25 Research Site Nanchang China 330006
    26 Research Site Nanchang China 330029
    27 Research Site Shandong China
    28 Research Site Shanghai China 200032
    29 Research Site Shanghai China 200080
    30 Research Site Shenyang China 110001
    31 Research Site TianJin China 300060
    32 Research Site Wuhan China 430022
    33 Research Site Wuhan China 430030
    34 Research Site Xi'an China 710061
    35 Research Site Yinchuan China 750004
    36 Research Site Zhengzhou China 450008
    37 Research Site Zhengzhou China
    38 Research Site Fukuoka-shi Japan 812-8582
    39 Research Site Hidaka-shi Japan 350-1298
    40 Research Site Kagoshima-shi Japan 890-8520
    41 Research Site Koto-ku Japan 135-8550
    42 Research Site Kurume-shi Japan 830-0011
    43 Research Site Maebashi-shi Japan 371-8511
    44 Research Site Morioka-shi Japan 028-3695
    45 Research Site Nagoya-shi Japan 464-8681
    46 Research Site Nakagami-gun Japan 903-0215
    47 Research Site Osaka-shi Japan 541-8567
    48 Research Site Sapporo-shi Japan 003-0804
    49 Research Site Sapporo-shi Japan 060-8638
    50 Research Site Shinjuku-ku Japan 160-8582
    51 Research Site Suita-shi Japan 565-0871
    52 Research Site Sunto-gun Japan 411-8777
    53 Research Site Toon-Shi Japan 791-0295
    54 Research Site Seoul Korea, Republic of 03080
    55 Research Site Seoul Korea, Republic of 03722
    56 Research Site Seoul Korea, Republic of 06351
    57 Research Site Seoul Korea, Republic of 5505
    58 Research Site Guadalajara Mexico 44650
    59 Research Site Guadalajra Mexico 44260
    60 Research Site Mexico Mexico 14080
    61 Research Site Lima Peru 15036
    62 Research Site Lima Peru 15038
    63 Research Site Barcelona Spain 08036
    64 Research Site Barcelona Spain 8035
    65 Research Site Cordoba Spain 14004
    66 Research Site Girona Spain 17007
    67 Research Site Hospitalet deLlobregat Spain 08907
    68 Research Site La Coruna Spain 15006
    69 Research Site Madrid Spain 28034
    70 Research Site Madrid Spain 28040
    71 Research Site Madrid Spain 28041
    72 Research Site Madrid Spain 28046
    73 Research Site Palma de Mallorca Spain 07010
    74 Research Site Valencia Spain 46009
    75 Research Site Kaohsiung city Taiwan 833
    76 Research Site Kaohsiung Taiwan 81362
    77 Research Site New Taipei Taiwan 220
    78 Research Site Taichung Taiwan 40705
    79 Research Site Tainan Taiwan
    80 Research Site Taipei Taiwan 10449
    81 Research Site Taipei Taiwan 11217
    82 Research Site Taoyuan Taiwan 333
    83 Research Site Ankara Turkey 06100
    84 Research Site Ankara Turkey 06490
    85 Research Site Istanbul Turkey 32098
    86 Research Site Istanbul Turkey 34214

    Sponsors and Collaborators

    • AstraZeneca
    • Gynecologic Oncology Group Foundation
    • European Network for Gynaecological Oncological Trial Groups

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT06079671
    Other Study ID Numbers:
    • D7984C00002
    • GOG-3092
    • ENGOT-cx19/GEICO
    • 165663
    • 2023-504374-38-00
    First Posted:
    Oct 12, 2023
    Last Update Posted:
    Oct 12, 2023
    Last Verified:
    Oct 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by AstraZeneca
    Locally Advanced Cervical Cancer;
    Adolescent and Young Adult;
    Volrustomig
    Additional relevant MeSH terms:
    Uterine Cervical Neoplasms

    Study Results

    No Results Posted as of Oct 12, 2023