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

Locally Advanced Cervical Cancer Clinical Trial

— eVOLVECervical  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06079671
• Other study ID #: D7984C00002
• Secondary ID: GOG-3092ENGOT-cx
• Status: Recruiting
• Phase: Phase 3
• Start date: September 22, 2023
• Est. completion date: October 24, 2029

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: October 24, 2029
• Est. primary completion date: February 19, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• Volrustomig
IV Infusion

Other:
• Placebo
IV Infusion

Locations

Country	Name	City	State
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Curitiba
Brazil	Research Site	Fortaleza
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Velho
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Teresina
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ste-Foy	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Changde
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Kunming
China	Research Site	Lanzhou
China	Research Site	Lanzhou
China	Research Site	Luzhou
China	Research Site	Nanchang
China	Research Site	Nanchang
China	Research Site	Shandong
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	TianJin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Yinchuan
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
Denmark	Research Site	Aarhus N
Denmark	Research Site	København Ø
Denmark	Research Site	Odense C
India	Research Site	Calicut
India	Research Site	Jaipur
India	Research Site	Lucknow
India	Research Site	Madurai
India	Research Site	Mohali
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	Vadodara
Italy	Research Site	Napoli
Italy	Research Site	Rome
Italy	Research Site	Turin
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kurume-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Morioka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nakagami-gun
Japan	Research Site	Osaka-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Toon-Shi
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Ciudad de México
Mexico	Research Site	Coyoacan
Mexico	Research Site	Culiacan
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajra
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Norway	Research Site	Oslo
Norway	Research Site	Trondheim
Peru	Research Site	Concepción
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Gliwice
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Puerto Rico	Research Site	San Juan
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Girona
Spain	Research Site	Hospitalet deLlobregat
Spain	Research Site	La Coruna
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung city
Taiwan	Research Site	New Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
United States	Research Site	Atlanta	Georgia
United States	Research Site	Augusta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Eugene	Oregon
United States	Research Site	Fort Worth	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	La Jolla	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Melrose Park	Illinois
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Providence	Rhode Island
United States	Research Site	Richmond	Virginia
United States	Research Site	Savannah	Georgia
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Syracuse	New York
United States	Research Site	Tucson	Arizona
United States	Research Site	Tyler	Texas
United States	Research Site	West Hollywood	California

Sponsors (3)

Lead Sponsor	Collaborator
AstraZeneca	European Network for Gynaecological Oncological Trial Groups, Gynecologic Oncology Group Foundation

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  China,  Denmark,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Norway,  Peru,  Poland,  Puerto Rico,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) in participants with PD-L1 expression based on the investigator assessment	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.	The study duration will be approximately 40 months.
Secondary	Progression-free Survival (PFS) in participants regardless of PD-L1 expression based on the investigator assessment	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.	The study duration will be approximately 40 months
Secondary	Overall Survival (OS) in participants regardless of PD-L1 expression.	OS defined as time from randomization until the date of death due to any cause.	The study duration will be approximately 6 years.
Secondary	Overall Survival (OS) in participants with PD-L1 expression	OS defined as time from randomization until the date of death due to any cause.	The study duration will be approximately 6 years.
Secondary	Objective Response Rate (ORR) in participants with PD-L1 expression/regardless of PD-L1 expression.	ORR is defined as the proportion of participants who have a CR or PR, as determined by Investigator per RECIST 1.1	The study duration will be approximately 40 months
Secondary	Duration of Response (DoR) in participants with a CR or PR in the PD-L1 expression analysis set/FAS.	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.	The study duration will be approximately 40 months
Secondary	Time to First Subsequent Therapy or death (TFST) in the PD-L1 expression analysis set/FAS	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.	The study duration will be approximately 40 months
Secondary	Time to second progression or death (PFS2) in the PD-L1 expression analysis set/FAS.	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.	The study duration will be approximately 6 years.
Secondary	PFS by BICR in the PD-L1 expression analysis set/FAS.	Endpoints based on the PFS by BICR assessment according to RECIST 1.1.	The study duration will be approximately 40 months
Secondary	The incidence of local progression, and distant disease progression as the first documented progression event in the PD-L1 expression analysis set/FAS.	Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence.	The study duration will be approximately 40 months
Secondary	PK of Volrustomig	Concentration of Volrustomig in serum.	The study duration will be approximately 40 months.
Secondary	The immunogenicity of volrustomig.	Incidence of ADAs against volrustomig in serum.	The study duration will be approximately 40 months
Secondary	Incidence of adverse events of Volrustomig compared to placebo;	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.	The study duration will be approximately 40 months.
Secondary	Participant-reported disease-related symptoms	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.	The study duration will be approximately 40 months.
Secondary	Participant-reported physical functioning	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.	The study duration will be approximately 40 months.
Secondary	Participant-reported global health status/Quality of Life.	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.	The study duration will be approximately 40 months.