Advanced Cervical Cancer MedDRA version: 21.1 Level: LLT Classification code 10008236 Term: Cervical cancer stage IV System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10008231 Term: Cervical cancer recurrent System Organ Class: 100000004864
Conditions
Sponsors
JSC BIOCAD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy all of the following criteria to be eligible for randomization: 1. Signing an IRB/EC-approved informed consent 2. Females = 18 years of age on day of signing informed consent 3. Histologically confirmed squamous carcinoma of the cervix 4. Progressing thru or recurrent disease treated for curative intent or primary metastatic cervical cancer stage FIGO IVB 5. Agreement to newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for determination of PD-L1 status prior to randomization (using archival biopsy material is only acceptable in subjects in whom obtaining a new sample is contraindicated) 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 7. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to use a contraceptive method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 92
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria must not be randomized: 1. Indications for potentially curative treatment (surgery or radiation therapy) 2. Prior systemic treatment for recurrent, secondarily progressive or initially metastatic disease 3. Previous use of chemotherapy other than initial treatment for curative intent (e.g. chemotherapy used concurrently with radiation therapy, neoadjuvant or consolidation chemotherapy cycles before radiotherapy or 2 chemotherapy cycles after completion of chemoradiotherapy are allowed) 4. Contraindications to cisplatin, carboplatin, paclitaxel, or bevacizumab 5. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with known brain metastases may participate provided that the brain metastases have been previously treated with radiotherapy or surgery only and are radiographically stable 6. Concomitant diseases or conditions which pose a risk of AE development during study treatment: a. uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg; b. stable angina functional class III-IV; c. unstable angina or myocardial infarction less than 6 months prior to randomization; d. NYHA Grade III–IV congestive heart failure; e. serious cardiac arrhythmia requiring medication (subjects with asymptomatic atrial fibrillation can be enrolled if controlled ventricular rate); f. atopic asthma, Stage III–IV COPD, angioedema; g. severe respiratory failure; h. any other diseases which pose unacceptable risk of AE development during study treatment in Investigator’s opinion. 7. Active or known or suspected autoimmune disease (subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll). 8. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to randomization. 9. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis 10. Neutrophils <1500/mcl or platelets <100 000/mcl or hemoglobin <90 g/l. 11. Creatinine = 1.5 x UNL. 12. Bilirubin = 1.5 x UNL (excluding Gilbert’s syndrome if bilirubin < 50 µmol/l) or AST/ALT = 3 x UNL (excluding subjects with liver metastases if AST/ALT < 5 x UNL) or alkaline phosphatase = 2.5 x UNL. 13. Chemotherapy or radiation therapy less than 28 days prior to randomization. 14. Major surgery procedure less than 28 days prior to randomization. 15. Previous use of PD-1/PD-L1/PD-L2 agent or another agent directed to stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX 40, CD137). 16. Previous use of VEGF/VEGFR inhibitors, including bevacizumab, ramucirumab, aflibercept and tyrosine kinase inhibitors. 17. Prior invasive malignancy with any evidence of disease within the last 3 years. Subjects with non-melanoma skin cancer or carcinoma in situ (e.g. breast cancer) who have undergone potentially curative therapy are not excluded. 18. Pre-existing clinically significant (= grade 2) peripheral neuropathy or hearing impairment 19. Any conditions or circumstances that limit subject’s ability to comply with protocol requirements 20. Active hepatitis B, active hepatitis ? or history of positive HIV. 21. Active infection requiring therapy or systemic antibiotics use less than 14 days prior to randomization. Severe infections within 28 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy (OS, PFS, ORR and others) of combination of BCD-100 and standard front-line therapy of advanced squamous cervical cancer consisting of platinum-based chemotherapy with or without bevacizumab at Investigator’s discretion (Test Regimen) in comparison with the same established standard regimen combined with placebo (Comparator Regimen).;Secondary Objective: To evaluate efficacy (OS, PFS, ORR and others) of Test Regimen versus Comparator Regimen according to PD-L1 status.;Primary end point(s): overall survival (OS) — the time from the date of randomization until death;Timepoint(s) of evaluation of this end point: continuously throughout the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival (PFS) per RECIST 1.1 — the time from the date of randomization until progression of disease according to RECIST 1.1 criteria or death PFS per iRECIST — the time from the date of randomization until progression of disease according to iRECIST criteria or death Overall response rate (ORR) per RECIST 1.1 ORR per iRECIST Disease control rate (DCR) Time to response (TTR) Duration of response (DOR);Timepoint(s) of evaluation of this end point: continuously throughout the trial | — |
Countries
Austria, Belgium, China, Czech Republic, Denmark, Finland, Georgia, Germany, Hungary, Poland, Romania, Russian Federation, Slovakia, Turkey
Contacts
Public ContactClinical Trials Department
JSC BIOCAD
Outcome results
None listed