Study of Volrustomig in Women with advanced Cervical Cancer who have not progressed following Chemoradiation Therapy
Scientific Title of Study
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)
Trial Acronym
eVOLVE Cervical
Secondary IDs if Any
Secondary ID
Identifier
D7984C00002 CSP V2.0 dated 07 August 2023
Protocol Number
NCT06079671
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head Site Management and Monitoring – India
Affiliation
AstraZeneca Pharma India Ltd
Address
AstraZeneca Pharma India Ltd.
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
Email
Sandeep.AV@astrazeneca.com
Details of Contact Person Scientific Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head Site Management and Monitoring – India
Affiliation
AstraZeneca Pharma India Ltd
Address
AstraZeneca Pharma India Ltd.
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
Email
Sandeep.AV@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head Site Management and Monitoring – India
Affiliation
AstraZeneca Pharma India Ltd
Address
AstraZeneca Pharma India Ltd.
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
Email
Sandeep.AV@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB
151 85 Sodertalje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Sodertalje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Countries of Recruitment
Brazil Canada China Denmark Germany India Italy Japan Mexico Norway Peru Poland Republic of Korea Spain Taiwan Turkey United Kingdom United States of America
Manavata Clinical Research Institute Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C539||Malignant neoplasm of cervix uteri, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
Placebo – route of administration is IV
Intervention
Volrustomig (MEDI5752)
Volrustomig – route of administration is IV
Inclusion Criteria
Age From
15.00 Year(s)
Age To
99.00 Year(s)
Gender
Female
Details
Inclusion Criteria
Screening Part I
Participants must have histologically confirmed cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma and the following requirements:
Participants must have histologically documented FIGO 2018 Stage IIIC to IVA cervical cancer (Appendix G); only participants with lymph node involvement will be included.
Nodal involvement confirmation may be either histological eg, biopsy or by imaging PET CT, CT or MRI with pathological lymph node size defined by a short axis diameter of 10 mm axial plane.
No evidence of metastatic disease M0.
Screening Part II
1 Participants must have completed concurrent chemoradiotherapy as defined below:
a. Completed within 1 to 56 days prior to randomization.
b. Received weekly cisplatin 40 mg m2 for 5 to 6 cycles as concurrent chemotherapy with radiation therapy. If participants cannot tolerate toxicity, must have received at least 4 cycles of cisplatin.
c. The last dose of cisplatin must be administered prior to, or concurrently with, the final dose of radiation. Consolidation chemotherapy after radiation is not permitted.
d. Received EBRT and brachytherapy as part of the chemoradiation therapy, and brachytherapy can only be omitted if there is a medical contraindication. Prescription doses of radiotherapy are requested as below:
i A total dose of 45 Gy for EBRT to the pelvis
ii If brachytherapy is used, normal tissues should be limited with 2 cc rectal dose 75 Gy, sigmoid 2 cc dose 75 Gy, and 2 cc bladder dose 90 Gy.
e.It is strongly preferred that participants complete CCRT within 8 weeks
ExclusionCriteria
Details
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1 As judged by the Investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.
2 Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer (ie, mucinous NOS, intestinal type, signet ring cell type, invasive stratified mucin producing carcinoma and gastric type) based on 2020 WHO classification of cervical cancer.
3 Evidence of metastatic disease (including metastasis to inguinal lymph nodes, intraperitoneal disease, lung liver, or bone; excluding metastasis to pelvic or paraaortic lymph nodes or vagina) prior to CCRT.
4 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 and of low potential risk for recurrence.
(b) Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease.
(c) Adequately treated carcinoma in situ without evidence of disease
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of volrustomig relative to placebo by assessment of PFS, in participants with PD L1 high expression
PFS is defined as the time from date of randomization until RECIST 1.1defined radiological progression or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier
Secondary Outcome
Outcome
TimePoints
To demonstrate the superiority of volrustomig relative to placebo by assessment of PFS, in participants regardless of PD L1 expression
PFS definition, measure of interest, and the events censoring rules are the same as per primary endpoint. The analysis will include all randomized participants regardless of PD L1 expression, as randomized
To demonstrate the superiority of volrustomig relative to placebo by assessment of OS, in participants regardless of PD L1 expression
OS defined as time from randomization until the date of death due to any cause.
The analysis will include all randomized participants regardless of PD L1 expression, as randomized. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anti cancer therapy
To demonstrate the superiority of volrustomig relative to placebo by assessment of OS, in participants with high expression of PDL1 expression
OS defined as time from randomization until the date of death due to any cause.
The analysis will include all randomized participants with high expression of PDL1, as randomized. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anti cancer therapy
To estimate the effectiveness of volrustomig relative to placebo by assessment of ORR in participants with PDL1 high expression regardless of PDL1 expression.
• ORR is defined as the proportion of participants who have a CR or PR, as determined by Investigator per RECIST 1.1
To estimate the effectiveness of volrustomig relative to placebo in terms of DoR in participants with a CR or PR in the PDL1 high 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
To estimate the effectiveness of volrustomig relative to placebo in terms of TFST in the PDL1 high 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
To estimate the effectiveness of volrustomig relative to placebo in terms of PFS2 in the PDL1 high expression analysis setFAS.
• 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.
To estimate the effectiveness of volrustomig relative to placebo in terms of PFS by BICR in the PDL1 high expression analysis set FAS
Endpoints based on the PFS by BICR assessment according to RECIST 1.1
To estimate the effectiveness of volrustomig relative to placebo on the incidence of local progression, and distant disease progression as the first documented progression event in the PDL1 high expression analysis set FAS.
Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence
To assess the PK of volrustomig.
Concentration of volrustomig in serum and PK parameters as data allow
To investigate the immunogenicity of volrustomig.
Incidence of ADAs against volrustomig in serum
To assess the safety and tolerability profile of volrustomig compared to placebo
AEs, clinical laboratory assessments, vital signs, and electrocardiograms.
To assess participant reported disease related symptoms in participants treated with volrustomig compared to placebo
Change from baseline as measured by the EORTC IL318 Symptom Experience subscale of the EORTC QLQ CX24.
The analysis will include all randomized participants.
The measure of interest will be mean change from baseline in disease related symptoms as measured by the EORTC IL318.
To assess participant reported physical functioning in participants treated with volrustomig versus placebo.
• Change from baseline of physical functioning as measured by the PROMIS SF PF 8c 7day.
The analysis will include all randomized participants.
The measure of interest will be mean change from baseline of physical functioning as measured by the PROMIS SF PF 8c.
To assess participant reported global health status QoL in participants treated with volrustomig versus placebo.
Change from baseline of GHS QoL as measured by the EORTC IL172.
The analysis will include all randomized participants.
The measure of interest will be mean change from baseline of GHS QoL as measured by the EORTC IL172.
Target Sample Size
Total Sample Size="1000" Sample Size from India="70" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Overall Design
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)
Participant Population:
Approximately 1430 participants with
high risk LACC who have not progressed following standard of care CCRT will be
screened, in order to randomize approximately 1000 participants in a 1:1 ratio
to two arms. Randomization will be stratified by PD L1 expression as assessed
by central laboratories using the investigational VENTANA PD L1 (SP263) Assay
(PD L1 high vs low/negative), FIGO stage (IIIC1 vs IIIC2 vs IVA), as well as
region (Asia vs non Asia).
Treatment Groups and
Duration:
Arm A: Volrustomig 750 mg IV on Day
1 of each 21 day cycle until RECIST 1.1 defined radiological progression or
histopathologically confirmed or up to 24 months (n = 500).
Arm B: Placebo IV on Day 1 of each
21 day cycle until RECIST 1.1 defined radiological progression or
histopathologically confirmed progression or up to 24 months (n = 500).
Participants will receive their
assigned treatment for up to 24 months, or until RECIST 1.1 defined
radiological progression or histopathologically confirmed progression by
Investigator assessment, unacceptable toxicity, withdrawal of consent, or
another discontinuation criterion is met. Treatment crossover is not allowed in
this study.