Clinical trial • Phase III • Oncology

VOLRUSTOMIG for Locally advanced cervical cancer

Phase III trial of VOLRUSTOMIG for Locally advanced cervical cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Locally advanced cervical cancer
Trial Stage
Phase III
Drug Modality
Monoclonal antibody|Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
31-10-2023
First CTIS Authorization Date
04-03-2024

Trial design

Randomised, experimental arm: volrustomig (medi5752) — intravenous (title: volrustomig (medi5752)). control arm: placebo (saline) — intravenous (title: placebo (saline)). dose and schedule not specified in the ctis record. Phase III trial across 40 sites in Norway, Spain, Germany and others.

Randomised
Yes
Comparator
Experimental arm: Volrustomig (MEDI5752) — intravenous (title: Volrustomig (MEDI5752)). Control arm: Placebo (saline) — intravenous (title: Placebo (saline)). Dose and schedule not specified in the CTIS record.
Target Sample Size
699
Trial Duration For Participant
2555

Eligibility

Recruits 699 paediatric patients.

Vulnerable Population
Adolescents/AYA are included (minimum age 15 years, participants <18 years require Tanner Stage III physical development). The protocol and application include AYA-specific informed consent/assent documentation and parent AYA consent forms (documents listed: L1_SIS and ICF_AYA ICF Part I/II, AYA ICF Part I/II Assent, and parent AYA consent documents). Inclusion requires capability to provide signed informed consent.

Inclusion criteria

  • {"criterion_text":"- Female."}
  • {"criterion_text":"- Capable of providing signed informed consent."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Body weight > 35 kg."}
  • {"criterion_text":"- Histologically confirmed cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, FIGO 2018 Stage IIIA to IVA cervical cancer, no evidence of metastatic disease."}
  • {"criterion_text":"- Initial staging procedures performed prior to initiation of any component of definitive treatment (CCRT)."}
  • {"criterion_text":"- Provision of FFPE tumor sample to assess the PD-L1 expression."}
  • {"criterion_text":"- Must not have progressed following CCRT, participants with persistent disease after definitive CCRT must not be amenable to other available therapies with curative intent."}
  • {"criterion_text":"- WHO/ECOG performance status of 0 or 1; duration of life expectancy of ≥ 12 weeks."}
  • {"criterion_text":"- Adequate organ and bone marrow function."}

Exclusion criteria

  • {"criterion_text":"- Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer."}
  • {"criterion_text":"- History of anaphylaxis to any biologic therapy or vaccine."}
  • {"criterion_text":"- 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); c) Physiologic doses of oral corticosteroids, ie, not exceeding 10 mg/day of prednisone (or equivalent) in the preceding 14 days."}
  • {"criterion_text":"- Patients who have undergone a previous hysterectomy, including a supracervical hysterectomy, or will have a hysterectomy as part of their initial cervical cancer therapy."}
  • {"criterion_text":"- Any prior (besides prior CCRT) or concurrent treatment for cervical cancer."}
  • {"criterion_text":"- Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery."}
  • {"criterion_text":"- Exposure to immune mediated therapy prior to the study for any indication."}
  • {"criterion_text":"- Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention."}
  • {"criterion_text":"- Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention."}
  • {"criterion_text":"- Evidence of metastatic disease."}
  • {"criterion_text":"- Intent to administer a fertility-sparing treatment regimen."}
  • {"criterion_text":"- History of organ transplant or allogenic stem cell transplant."}
  • {"criterion_text":"- History of active primary immunodeficiency or active or prior documented autoimmune or inflammatory disorders."}
  • {"criterion_text":"- Uncontrolled intercurrent illness."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Unresolved toxicities from previous CCRT except for irreversible toxicity that is not reasonably expected to be exacerbated."}
  • {"criterion_text":"- Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression-free Survival (PFS) based on the investigator assessment in all randomized participants (FAS).","definition_or_measurement_approach":"Based on the investigator assessment in all randomized participants (Full Analysis Set)."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS defined as time from randomization to RECIST 1.1-defined radiological progression or histopathologically confirmed progression as assessed by the Investigator, or death from any cause, whichever occurs earlier."}
  • {"endpoint_text":"- Up to approximately 7 years","definition_or_measurement_approach":"Follow-up duration for assessment: up to approximately 7 years."}

Secondary endpoints

  • {"endpoint_text":"- Overall Survival (OS) in all randomized participants. OS defined as time from randomization until the date of death due to any cause.","definition_or_measurement_approach":"OS: time from randomization until date of death due to any cause."}
  • {"endpoint_text":"- Objective Response Rate (ORR) in all randomized participants. ORR is defined as the proportion of participants who have a CR or PR, as determined by the Investigator per RECIST 1. 1.","definition_or_measurement_approach":"ORR: proportion of participants with complete response (CR) or partial response (PR) per Investigator assessment using RECIST 1.1."}
  • {"endpoint_text":"- Duration of Response (DoR) in all randomized participants. DoR in participants with a CR or PR: Time from the date of first detection of CR or PR until the date of RECIST 1. 1- defined radiological progression or histopathologically confirmed progression.","definition_or_measurement_approach":"DoR: time from first detection of CR or PR until RECIST 1.1-defined radiological progression or histopathologically confirmed progression."}
  • {"endpoint_text":"- Time to First Subsequent Therapy or death (TFST) in all randomized participants. 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.","definition_or_measurement_approach":"TFST: time from randomization to start date of first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death."}
  • {"endpoint_text":"- Time to second progression or death (PFS2) in all randomized participants. PFS2: The time from randomization to the earliest of the progression event (following the initial Investigator-assessed progression), after the first subsequent therapy, or death. The date of the second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice.","definition_or_measurement_approach":"PFS2: time from randomization to earliest of second progression after first subsequent therapy, or death; second progression recorded in eCRF per local clinical practice."}
  • {"endpoint_text":"- PFS by BICR in all randomized participants. Endpoints based on the PFS by BICR assessment according to RECIST 1.1.","definition_or_measurement_approach":"PFS assessed by blinded independent central review (BICR) according to RECIST 1.1."}
  • {"endpoint_text":"- The incidence of local progression, and distant disease progression as the first documented progression event in all randomized participants. Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence.","definition_or_measurement_approach":"Incidence: number and percentage of participants with local progression or distant disease recurrence as first documented progression event."}
  • {"endpoint_text":"- PK of volrustomig The concentration of volrustomig in serum and PK parameters.","definition_or_measurement_approach":"Pharmacokinetics: serum concentration of volrustomig and PK parameters."}
  • {"endpoint_text":"- The immunogenicity of volrustomig. Incidence of ADAs against volrustomig in serum.","definition_or_measurement_approach":"Immunogenicity: incidence of anti-drug antibodies (ADAs) against volrustomig in serum."}
  • {"endpoint_text":"- Safety and tolerability profile of volrustomig compared to placebo. AEs, clinical laboratory assessments, vital signs, and electrocardiograms.","definition_or_measurement_approach":"Safety assessments: adverse events, clinical laboratory tests, vital signs, ECGs."}
  • {"endpoint_text":"- Participant-reported disease-related symptoms. Change from baseline as measured by the EORTC IL318 (Symptom Experience subscale of the EORTC QLQ-CX24).","definition_or_measurement_approach":"PROs: change from baseline measured by EORTC IL318 (Symptom Experience subscale of EORTC QLQ-CX24)."}
  • {"endpoint_text":"- Participant reported physical functioning Change from baseline of physical functioning as measured by the PROMIS SF-PF Sc 7-day.","definition_or_measurement_approach":"PROs: change from baseline in physical functioning measured by PROMIS SF-PF 7-day."}
  • {"endpoint_text":"- Participant-reported global health status/QoL. Change from baseline of GHS/QoL as measured by the EORTC Ill 72.","definition_or_measurement_approach":"PROs: change from baseline in global health status/quality of life measured by EORTC IL172."}
  • {"endpoint_text":"- Up to approximately 7 years","definition_or_measurement_approach":"Follow-up duration for secondary endpoints: up to approximately 7 years."}

Recruitment

Planned Sample Size
699
Recruitment Window Months
84
Consent Approach
Adults must be capable of providing signed informed consent. Adolescents/AYA (minimum age 15) are included; participants <18 years require Tanner Stage III physical development. AYA-specific informed consent and assent processes are provided (documents listed in CTIS: AYA ICF Part I/II, AYA ICF Part I/II Assent, parent AYA consent Part I/II). Subject information and ICF documents are available in multiple language versions (examples in the record: English, Norwegian, Spanish, Italian, Polish, German, Danish).

Geography

Total Number Of Sites
40
Total Number Of Participants
101

Norway

Earliest CTIS Part Ii Submission Date
12-02-2024
Latest Decision Or Authorization Date
08-03-2024
Processing Time Days
25
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
St. Olavs Hospital HF
Department Name
Department of Obstetrics and Gynecology
Contact Person Name
Guro Aune
Contact Person Email
guro.aune@stolav.no
Site Name
Oslo University Hospital HF
Department Name
Department of Gynaecological Oncology
Contact Person Name
Kristina Lindemann
Contact Person Email
klinde@ous-hf.no
Site Name
Universitetssykehuset Nord-Norge HF
Department Name
Department of Gynecology Oncology
Contact Person Name
Anne Gry Bentzen
Contact Person Email
anne.gry.bentzen@unn.no

Spain

Earliest CTIS Part Ii Submission Date
08-04-2025
Latest Decision Or Authorization Date
15-04-2025
Processing Time Days
7
Number Of Sites
10
Number Of Participants
20

Sites

Site Name
Institut Catala D'oncologia
Department Name
Oncology department
Contact Person Name
Beatriz Pardo Bufalo
Contact Person Email
bpardo@iconcologia.net
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology department
Contact Person Name
Roberta Mazzeo
Contact Person Email
robertamazzeo@vhio.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology department
Contact Person Name
Luis Manso
Contact Person Email
luismansosanchez@gmail.com
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Oncology department
Contact Person Name
Ignacio Romero
Contact Person Email
iromero@fivo.org
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Oncology department
Contact Person Name
Eva Lindemann
Contact Person Email
eva_m_guerra@hotmail.com
Site Name
Institut Catala D'oncologia
Department Name
Oncology department
Contact Person Name
Pilar Barretina
Contact Person Email
mpbarretina@iconcologia.net
Site Name
Hospital Universitario Reina Sofia
Department Name
Oncology department
Contact Person Name
Maria Jesus Rubio
Contact Person Email
mjesusrubio63@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology department
Contact Person Name
Lydia Gaba
Contact Person Email
lgaba@clinic.cat
Site Name
Hospital Clinico San Carlos
Department Name
Oncology Department
Contact Person Name
Gloria Marquina
Contact Person Email
gloriamarquina@gmail.com
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncology department
Contact Person Name
Maria Quindos
Contact Person Email
Maria.quindos.varela@sergas.es

Germany

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
05-06-2024
Processing Time Days
128
Number Of Sites
4
Number Of Participants
4

Sites

Site Name
KEM I Evang. Kliniken Essen-Mitte gGmbH
Department Name
Gynäkologisches Krebszentrum
Contact Person Name
Florian Heitz
Contact Person Email
f.heitz@kem-med.com
Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Frauenheilkunde
Contact Person Name
Bahriye Aktas
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Gynäkologie
Contact Person Name
Jalid Sehouli
Contact Person Email
jalid.sehouli@charite.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Frauenklinik
Contact Person Name
Linn Wölber
Contact Person Email
lwoelber@uke.de

Italy

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
11-03-2024
Processing Time Days
42
Number Of Sites
12
Number Of Participants
40

Sites

Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
Oncologia
Contact Person Name
Giorgio Valabrega
Contact Person Email
giorgio.valabrega@unito.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
U.O.C. Ginecologia Oncologica
Contact Person Name
Vanda Salutari
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.C. Ginecologia Oncologica
Contact Person Name
Francesco Raspagliesi
Site Name
Azienda Ospedaliera Per L'Emergenza Cannizzaro
Department Name
Oncologia Medica
Contact Person Name
Giuseppa Scandurra
Site Name
Humanitas Mirasole S.p.A.
Department Name
Head of Gynecologic Oncology Unit of Humanitas San Pio X Hospital
Contact Person Name
Domenica Lorusso
Contact Person Email
Domenica.Lorusso@hunimed.eu
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Oncologia
Contact Person Name
Stefania Canova
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Uro-Ginecologia Oncologica
Contact Person Name
Carmela Pisano
Contact Person Email
c.pisano@istitutotumori.na.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
U.O.C. Ginecologia Chirurgica ed Oncologica
Contact Person Name
Federica Tomao
Contact Person Email
federica.tomao@uniroma1.it
Site Name
European Institute Of Oncology S.r.l.
Department Name
Ginecologia Oncologica
Contact Person Name
Nicoletta Colombo
Contact Person Email
nicoletta.colombo@ieo.it
Site Name
Careggi University Hospital
Department Name
Ginecologia Medica Oncologica
Contact Person Name
Maria Cristina Petrella
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Ematologia ed Oncologia Medica
Contact Person Name
Claudio Zamagni
Contact Person Email
`claudio.zamagni@aosp.bo.it
Site Name
Alessandro Manzoni Hospital
Department Name
Oncologia
Contact Person Name
Antonio Ardizzoia
Contact Person Email
a.ardizzoia@asst-lecco.it

Denmark

Earliest CTIS Part Ii Submission Date
12-02-2024
Latest Decision Or Authorization Date
04-03-2024
Processing Time Days
21
Number Of Sites
3
Number Of Participants
7

Sites

Site Name
Odense University Hospital
Department Name
Department of Oncology
Contact Person Name
Anja Ør Knudsen
Contact Person Email
Anja.Oer.knudsen@rsyd.dk
Site Name
Region Midtjylland
Department Name
Department of Oncology
Contact Person Name
Christian Wulff
Contact Person Email
chriwulf@rm.dk
Site Name
Rigshospitalet
Department Name
Department of Oncology
Contact Person Name
Trine Jakobi Nøttrup

Poland

Earliest CTIS Part Ii Submission Date
06-02-2024
Latest Decision Or Authorization Date
08-03-2024
Processing Time Days
31
Number Of Sites
8
Number Of Participants
26

Sites

Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Ginekologii Onkologicznej
Contact Person Name
Mariusz Bidzinski
Contact Person Email
Mariusz.Bidzinski@nio.gov.pl
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Poloznictwa i Ginekologii, Ginekologii Onkologicznej i Endokrynologii Ginekologicznej
Contact Person Name
Dagmara Klasa-Mazurkiewicz
Contact Person Email
dklasa@gumed.edu.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy (Gliwice)
Department Name
III Klinika Radioterapii i Chemioterapii
Contact Person Name
Rafal Tarnawski
Site Name
Bialostockie Centrum Onkologii Im. Marii Sklodowskiej-Curie W Bialymstoku
Department Name
Oddzial Onkologii Ginekologicznej
Contact Person Name
Beata Mackowiak-Matejczyk
Site Name
Wielkopolskie Centrum Onkologii Im. Marii Sklodowskiej-Curie
Department Name
Oddzial Radioterapii i Onkologii Ginekologicznej
Contact Person Name
Bartosz Urbanski
Contact Person Email
Bartosz.urbanski@wco.pl
Site Name
Dolnoslaskie Centrum Onkologii Pulmonologii I Hematologii
Department Name
III Klinika Radioterapii i Chemioterapii
Contact Person Name
Bozena Cybulska-Stopa
Contact Person Email
bozena.cybulska@dcopih.pl
Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Osrodek Onkologii i Hematologii Zaklad Teleradioterapii
Contact Person Name
Jacek Fijuth
Contact Person Email
jacekf@kopernik.lodz.pl
Site Name
Jagiellońskie Centrum Innowacji Sp. z o.o.
Contact Person Name
Pawel Blecharz
Contact Person Email
pawel.blecharz@interia.pl

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
volrustomig
Active Substance
VOLRUSTOMIG
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus: 1
Investigational Product Name
Saline
Modality
Other

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