Locally Advanced Cervical Cancer Clinical Trial
— eVOLVECervicalOfficial 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)
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca | European Network for Gynaecological Oncological Trial Groups, Gynecologic Oncology Group Foundation |
United States, Brazil, Canada, China, Denmark, India, Italy, Japan, Korea, Republic of, Mexico, Norway, Peru, Poland, Puerto Rico, Spain, Taiwan, Turkey,
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. |
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