CTRI/2024/01/061598
Not yet recruiting
Phase 3
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)
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- AstraZeneca AB
- Enrollment
- 1,000
- Locations
- 10
- Primary Endpoint
- To demonstrate the superiority of volrustomig relative to placebo by assessment of PFS, in participants with PD L1 high expression
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Eligibility Criteria
- Ages
- 15.00 Year(s) to 99.00 Year(s) (—)
- Sex
- Female
Inclusion Criteria
- •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 M
- •Screening Part II 1 Participants must have completed concurrent chemoradiotherapy as defined below: a.
- •Completed within 1 to 56 days prior to randomization.
- •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.
- •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.
- •Received EBRT and brachytherapy as part of the chemoradiation therapy, and brachytherapy can only be omitted if there is a medical contraindication.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
To demonstrate the superiority of volrustomig relative to placebo by assessment of PFS, in participants with PD L1 high expression
Time Frame: 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 Outcomes
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
Investigators
Mr Sandeep AV
AstraZeneca Pharma India Ltd
Study Sites (10)
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