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)

Phase 3

Not yet recruiting

• Conditions: D069 Cervix, unspecified; Cervix, unspecified; D069

• Registration Number: PER-044-23
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-13
• Last Update Posted: 2024-08-20

Recruitment & Eligibility

• Status: Without starting enrollment
• Sex: Female
• Target Recruitment: 0

Inclusion Criteria

1Participant must be = 15 years at the time of screening.
Participants < 18 years of age: Physical changes should be aligned with Tanner stage III.

2Participants 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).

3Initial staging procedures performed prior to initiation of any component of definitive treatment (CCRT) should include:
Pelvic MRI (preferred) or CT with IV contrast.
Chest/abdomen CT (preferred) or MRI with IV contrast.
PET CT is recommended in addition but not mandatory.
Brain MRI (preferred) or CT with IV contrast only if symptomatic.
The above scans for initial staging procedures must have been performed no more than 42 days prior to the first dose of CCRT.

4Provision of FFPE tumor sample to assess the PD L1 expression as determined by a central laboratory using the VENTANA PD L1 (SP263) Assay prior to randomization. Patients with unknown PD L1 expression are not eligible for study.
Tumor sample requirements as follows: FFPE sample must be collected less than 3 months prior to to the first dose of CCRT.

5Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the pre screening informed consent form (Screening Part I ICF) as described in Appendix A, which includes compliance with the requirements and restrictions listed in the ICF and this protocol. Provision of signed and dated written Part I screening ICF prior to any mandatory study specific procedures and analyses is required.

1Participants must have completed concurrent chemoradiotherapy as defined below:
a.Completed within 1 to 56 days prior to randomization and the first dose of the study intervention.
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 p

Exclusion Criteria

1As judged by the Investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.

2Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer.

3Evidence 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.

4History 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.

5Unresolved toxicities from previous CCRT, defined as toxicities not yet resolved to NCI CTCAE 5.0 Grade = 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by the study intervention in the opinion of the Investigator may be included (eg, hearing loss, alopecia and NCI CTCAE 5.0 Grade 2 peripheral neuropathy).

6Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula.

7History of organ transplant

8Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (eg, colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, pneumonitis (past medical history of ILD, drug induced ILD, or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD), etc. The following are exceptions to this criterion:
(a)Participants with vitiligo or alopecia.
(b)Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
(c)Any chronic skin condition that does not require systemic therapy.
(d)Participants without active disease in the last 5 years prior to enrolment may be included but only after consultation with the Study Clinical Lead.
(e)Participants with celiac disease controlled by diet alone.

Study & Design

• Study Type: Interventional
• Study Design: Not specified