Efficacy and Safety of BCD-100 (Anti-PD-1) in Combination With Platinum-Based Chemotherapy With and Without Bevacizumab as First-Line Treatment of Subjects With Advanced Cervical Cancer (FERMATA)

NCT ID: NCT03912415

Last Updated: 2020-09-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

316 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-01

Study Completion Date

2024-12-01

Brief Summary

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This is a randomized, multicenter, double-blind, Phase 3 study of efficacy and safety of BCD-100 plus platinum-based chemotherapy with and without bevacizumab versus placebo plus platinum-based chemotherapy with and without bevacizumab

Detailed Description

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Subjects will be randomized in a 1:1 ratio to receive either Test Regimen or Comparator Regimen as the first-line treatment for advanced cervical cancer. Subjects will receive study therapy Q3W until progression of the disease or signs of unacceptable toxicity. In the absence of dose-limiting toxicity chemotherapy should be continued for at least 6 cycles, then, upon Investigator's decision and/or subjects' wish, the use of chemotherapy can be stopped while maintenance therapy with BCD-100/Placebo with or without bevacizumab (depending on initial therapy choice) continues until disease progression.

Conditions

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Cervical Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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BCD-100

BCD-100 3 mg/kg Q3W

Group Type EXPERIMENTAL

BCD-100

Intervention Type BIOLOGICAL

Anti-PD-1 monoclonal antibody, IV infusion

Bevacizumab

Intervention Type BIOLOGICAL

IV infusion

Paclitaxel

Intervention Type DRUG

IV infusion

Cisplatin (or Carboplatin)

Intervention Type DRUG

IV infusion

Placebo

Group Type PLACEBO_COMPARATOR

Bevacizumab

Intervention Type BIOLOGICAL

IV infusion

Paclitaxel

Intervention Type DRUG

IV infusion

Cisplatin (or Carboplatin)

Intervention Type DRUG

IV infusion

Placebo

Intervention Type OTHER

Placebo

Interventions

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BCD-100

Anti-PD-1 monoclonal antibody, IV infusion

Intervention Type BIOLOGICAL

Bevacizumab

IV infusion

Intervention Type BIOLOGICAL

Paclitaxel

IV infusion

Intervention Type DRUG

Cisplatin (or Carboplatin)

IV infusion

Intervention Type DRUG

Placebo

Placebo

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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 \< 1% per year from the moment of signing informed consent, during the treatment period and at least 6 months after administration of the last dose of study drug. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes, and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include but are not limited to bilateral tubal ligation and/or occlusion, male sterilization, and intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) is not acceptable method of contraception.

Exclusion Criteria

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:

1. uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 90 mm Hg;
2. stable angina functional class III-IV;
3. unstable angina or myocardial infarction less than 6 months prior to randomization;
4. NYHA Grade III-IV congestive heart failure;
5. serious cardiac arrhythmia requiring medication (subjects with asymptomatic atrial fibrillation can be enrolled if controlled ventricular rate);
6. atopic asthma, Stage III-IV COPD, angioedema;
7. severe respiratory failure;
8. 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 С or history of positive HIV.
21. Active infection requiring therapy or systemic antibiotics use less than 14 days prior to enrollment. Severe infections within 28 days prior to first study drug administration.
22. Administration of a live vaccine within 28 days prior to enrollment
23. Current using of another investigational device or drug study, or less than 30 days since ending of using of another investigational device or drug study
24. Life expectancy less than 12 weeks
25. Significant adverse events (AE) of previous therapy excluding chronic and/or irreversible events which cannot affect study drug safety evaluation (e.g. alopecia)
26. Known hypersensitivity or allergy to paclitaxel, cisplatin, carboplatin, bevacizumab, BCD-100 or any of their excipients. Known hypersensitivity or allergy to drugs derived from Chinese hamster (CHO) ovary cells or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
27. Pregnancy or breast-feeding
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Biocad

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yulia N Linkova, MD, PhD

Role: STUDY_DIRECTOR

Director of Clinical Development Department, BIOCAD

Locations

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Shanghai Tenth People's Hospital

Shanghai, , China

Site Status RECRUITING

High technology Hospital Medcenter

Batumi, , Georgia

Site Status RECRUITING

Acad. F.Todua Medical center "Research institute of Clinical Medicine"

Tbilisi, , Georgia

Site Status RECRUITING

High Technology Medical Centre, University Clinic

Tbilisi, , Georgia

Site Status RECRUITING

Institute for Personalized Medicine Ltd.

Tbilisi, , Georgia

Site Status RECRUITING

Institute of Clinical Oncology

Tbilisi, , Georgia

Site Status RECRUITING

LEPL First University Clinic of Tbilisi State Medical University

Tbilisi, , Georgia

Site Status RECRUITING

Multiprofile Clinic Consilium Medulla

Tbilisi, , Georgia

Site Status RECRUITING

Neo Medi

Tbilisi, , Georgia

Site Status RECRUITING

City Hospital No. 5

Barnaul, , Russia

Site Status RECRUITING

Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky

Krasnoyarsk, , Russia

Site Status RECRUITING

Moscow Clinical Scientific and Practical Center named A.S. Loginova

Moscow, , Russia

Site Status RECRUITING

N.N. Blokhin National Medical Research Center of Oncology (2)

Moscow, , Russia

Site Status RECRUITING

State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department

Moscow, , Russia

Site Status RECRUITING

Murmansk Regional Clinical Hospital named after P.A. Bayandina

Murmansk, , Russia

Site Status RECRUITING

Clinical Oncology Dispensary

Omsk, , Russia

Site Status RECRUITING

LLC "New Clinic"

Pyatigorsk, , Russia

Site Status RECRUITING

AV Medical Group

Saint Petersburg, , Russia

Site Status RECRUITING

JSC "Modern Medical Technologies"

Saint Petersburg, , Russia

Site Status RECRUITING

N.N. Petrov National Medical Research Center of Oncology (2)

Saint Petersburg, , Russia

Site Status RECRUITING

Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)

Saint Petersburg, , Russia

Site Status RECRUITING

Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "

Saransk, , Russia

Site Status RECRUITING

Stavropol Regional Clinical Oncology Center

Stavropol, , Russia

Site Status RECRUITING

Regional Clinical Oncology Hospital

Yaroslavl, , Russia

Site Status RECRUITING

Sverdlovsk Regional Oncology Center

Yekaterinburg, , Russia

Site Status RECRUITING

Memorial Şişli Istanbul

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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China Georgia Russia Turkey (Türkiye)

Central Contacts

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Sergey N Fogt, MD, PhD

Role: CONTACT

+7-(812)-380-49-33

Fedor B Krykov, MD, PhD

Role: CONTACT

+7-(812)-380-49-33

Facility Contacts

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Zheng-yu Lu, MD

Role: primary

Tamta Makharadze, MD

Role: primary

Tamar Melkadze, MD

Role: primary

Miranda Gogishvili, MD

Role: primary

Alexandre Tavartkiladze, MD, PhD

Role: primary

Gia Nemsadze, MD, PhD

Role: primary

Nana Chikhladze, MD

Role: primary

David Karsimashvili, MD

Role: primary

Mikheil Shavdia, MD

Role: primary

Denis A Tancyirev, MD

Role: primary

Ruslan A Zukov, MD, PhD

Role: primary

Ludmila G Zhukova, MD, PhD

Role: primary

Elena V Artamonova, MD, PhD

Role: primary

Daniil Stroyakovsky, MD

Role: primary

Evgeny A Fomin, MD

Role: primary

Mikhail V Dvorkin, MD, PhD

Role: primary

Valery M Chistyakov, MD, PhD

Role: primary

Timur T Andabekov, MD, PhD

Role: primary

Svetlana V Odintsova, MD

Role: primary

Adilia F Urmancheeva, MD, PhD

Role: primary

Vladimir M Moiseenko, MD, PhD

Role: primary

Pavel Skopin, PhD

Role: primary

Oksana N Shkodenko, MD

Role: primary

Nikolay V Kislov, MD, PhD

Role: primary

Dmitry E Emelyanov, MD, PhD

Role: primary

Fazilet E Dinsbas, MD

Role: primary

Other Identifiers

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BCD-100-5

Identifier Type: -

Identifier Source: org_study_id

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