Efficacy and Safety of BCD-100 (Anti-PD-1) in Combination With Platinum-Based Chemotherapy and Bevacizumab in Patients With Recurrent, Persistent or Metastatic Cervical Cancer (CAESURA)

May 8, 2019 updated by: Biocad

Multicenter Open-Label Single-Arm Trial of the Efficacy and Safety of BCD-100 in Combination With Platinum-Based Chemotherapy and Bevacizumab as First Line Treatment in Patients With Recurrent, Persistent or Metastatic Cervical Cancer

This is a multicenter, open-label, single-arm study of efficacy, safety and pharmacokinetics of BCD-100 (JSC BIOCAD, Russia) in combination with platinum-based chemotherapy and bevacizumab as first-line treatment in patients with recurrent/persistent or metastatic cervical cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The study will be conducted in two stages. At the first stage patients will receive up to 6 cycles of BCD-100 in combination with platinum-based chemotherapy and bevacizumab or until unacceptable toxicity or disease progression. Patients who have demonstrated a positive antitumor effect (stabilization of the disease, partial or complete response) and who have no signs of unacceptable toxicity could continue to receive up to 12 cycles of maintenance therapy of BCD-100 in combination with bevacizumab or until unacceptable toxicity or disease progression.

Study Type

Interventional

Enrollment (Anticipated)

49

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 111123
        • Recruiting
        • Moscow Clinical Scientific and Practical Center named A.S. Loginova
        • Contact:
          • Ludmila G Zhukova, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Moscow, Russian Federation, 115478
        • Recruiting
        • N.N. Blokhin National Medical Research Center of Oncology (2)
        • Contact:
          • Elena V Artamonova, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Moscow, Russian Federation, 115478
        • Recruiting
        • N.N. Blokhin National Medical Research Center of Oncology
        • Contact:
          • Sergey A Tulandin, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Moscow, Russian Federation, 123056
        • Recruiting
        • JSC "MEDSI Group of Companies"
        • Contact:
          • Evgeny V Ledin, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Moscow, Russian Federation, 143423
        • Recruiting
        • Moscow City Oncology Hospital No. 62
        • Contact:
          • Daniil L Stroyakovsky, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Saint Petersburg, Russian Federation, 197758
        • Recruiting
        • N.N. Petrov National Medical Research Center of Oncology
        • Contact:
          • Tatyana Y Semiglazova, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Saint Petersburg, Russian Federation, 190013
        • Recruiting
        • JSC "Modern medical technologies"
        • Contact:
          • Svetlana V Odintsova, MD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Saint Petersburg, Russian Federation, 197758
        • Recruiting
        • Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
        • Contact:
          • Vladimir M Moiseenko, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Saint Petersburg, Russian Federation, 197082
        • Recruiting
        • LLC "AB Medical Group"
        • Contact:
          • Timor T Andabekov, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Altai Krai
      • Barnaul, Altai Krai, Russian Federation, 656045
        • Recruiting
        • City Hospital No. 5
        • Contact:
          • Denis A Tancyirev, MD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Arkhangelsk Oblast
      • Arkhangel'sk, Arkhangelsk Oblast, Russian Federation, 163045
        • Recruiting
        • Arkhangelsk Clinical Oncology Dispensary
        • Contact:
          • Marina N Nechaeva, MD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Chelyabinsk Oblast
      • Chelyabinsk, Chelyabinsk Oblast, Russian Federation, 454087
        • Recruiting
        • Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
        • Contact:
          • Natalya V Fadeeva, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Kaluga Oblast
      • Obninsk, Kaluga Oblast, Russian Federation, 249036
        • Recruiting
        • National Medical Radiology Research Center
        • Contact:
          • Natalya A Fetisova, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Krasnodar Kari
      • Krasnodar, Krasnodar Kari, Russian Federation, 350040
        • Recruiting
        • Clinical Oncologic Dispensary No. 1
        • Contact:
    • Krasnoyarsk Krai
      • Krasnoyarsk, Krasnoyarsk Krai, Russian Federation, 660133
        • Recruiting
        • Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky
        • Contact:
          • Ruslan A Zukov, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Murmansk Oblast
      • Murmansk, Murmansk Oblast, Russian Federation, 183047
        • Recruiting
        • Murmansk Regional Clinical Hospital named after P.A. Bayandina
        • Contact:
    • Omsk Oblast
      • Omsk, Omsk Oblast, Russian Federation, 644013
        • Recruiting
        • Clinical Oncology Dispensary
        • Contact:
          • Mikhail V Dvorkin, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Republic Of Mordovia
      • Saransk, Republic Of Mordovia, Russian Federation, 430005
        • Recruiting
        • Republican Oncology Center
        • Contact:
          • Pavel I Skopin, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Republic Of Tatarstan
      • Kazan, Republic Of Tatarstan, Russian Federation, 420029
        • Recruiting
        • Republican Clinical Oncology Cente
        • Contact:
          • Yana F Shasamutdinova, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Saint-Petersburg
      • Saint Petersburg, Saint-Petersburg, Russian Federation, 197758
        • Recruiting
        • N.N. Petrov National Medical Research Center of Oncology (2)
        • Contact:
          • Adilia F Urmancheeva, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Stavropol Krai
      • Pyatigorsk, Stavropol Krai, Russian Federation, 357500
        • Recruiting
        • LLC "New Clinic"
        • Contact:
          • Valery M Chistyakov, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
      • Stavropol', Stavropol Krai, Russian Federation, 355047
        • Recruiting
        • Stavropol Regional Clinical Oncology Center
        • Contact:
          • Oksana N Shkodenko, MD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Sverdlovsk Oblast
      • Ekaterinburg, Sverdlovsk Oblast, Russian Federation, 620036
        • Recruiting
        • Sverdlovsk Regional Oncology Center
        • Contact:
          • Dmitry E Emelyanov, MD, PhD
          • Phone Number: +7-(812)-380-49-34
          • Email: biocad@biocad.ru
    • Yaroslavskaya Oblast
      • Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150054
        • Recruiting
        • Regional Clinical Oncology Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Signed Informed Consent Form and the subject's ability to follow the Protocol requirements;
  2. Age: 18 years and older at the signing of the informed consent;
  3. Histologically verified (documented) adenomatous, adenosquamous, or squamous cervical cancer;
  4. Newly diagnosed metastatic cervical cancer or recurrent/persistent cervical cancer;
  5. Availability of archival histological tumor material (paraffin blocks) or consent to biopsy;
  6. ECOG performance status of 0 or 1;
  7. At least one RESICT 1.1-defined measurable target lesion confirmed by an independent review;
  8. Patients with reproductive potential must agree to practice acceptable methods of birth control throughout the entire trial period, starting from signing the informed consent and up to 24 weeks after the last dose of investigational product.

Exclusion Criteria:

  1. Indications for radical therapy (surgical or radiotherapy);
  2. Prior systemic treatment for recurrent, secondarily progressive or initially metastatic disease;
  3. Chemotherapy, and / or radiation therapy, and / or chemo-radiation therapy for early stages of cervical cancer with disease progression / recurrence earlier than 6 months after the end of therapy;
  4. Patients with severe concomitant factors or the effects of their treatment (hemorrhage, perforation, fistula);
  5. Central nervous system (CNS) metastases;

  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. atopic asthma, Stage III-IV COPD, angioedema;
    6. severe respiratory failure;
    7. 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. Established diagnosis of coagulopathy and / or clinically significant bleeding, including nasal bleeding;
  10. The need for regular intake of anticoagulants, antiplatelet agents, platelet function inhibitors, or their course application less than 1 month before being included in the study;
  11. Hematologic disorders: neutrophils <1500/mcl or platelets <100 000/mcl or hemoglobin <90 g/l;
  12. Renal disorders: creatinine ≥ 1.5 x UNL;
  13. Hepatic disorders: 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 ≥ 5 x UNL;
  14. Any anti-cancer therapy less than 28 days prior to randomization;
  15. Previous use of PD-1/PD-L1/PD-L2/CTLA-4 agent;
  16. Previous use of VEGF/VEGFR inhibitors, including bevacizumab, ramucirumab, aflibercept and tyrosine kinase inhibitors;
  17. Concomitant cancer (except for cervical carcinoma in situ after radical surgery or basal cell/ squamous cell carcinoma after radical surgery);
  18. Clinically significant (≥2 degree) peripheral neuropathy or hearing impairment;
  19. Any condition that prevents a patient from following the Protocol procedures (dementia, neurological or mental disorders, drug/alcohol abuse, etc.);
  20. Simultaneous participation in other clinical trials , participation in other clinical trials within 30 days prior to the first dose of the investigational product;
  21. Acute infection or the acute phase of chronic infection within 28 days prior the first dose of the investigational product;
  22. Active HBV/HCV/HIV infection, active syphilis;
  23. Patients unable to receive an IV infusions;
  24. Patients unable to receive an IV contrast agent;
  25. Hypersensitivity to any of the components of BCD-100, bevacizumab, paclitaxel, cisplatin (or carboplatin);
  26. Life expectancy less than 6 months;
  27. Significant adverse events (AE) of previous therapy excluding chronic and/or irreversible events which cannot affect study drug safety evaluation (e.g. alopecia);
  28. Pregnancy or breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BCD-100
BCD-100 mg/kg Q3W
Drug: Paclitaxel
IV infusion
Biological: BCD-100
Anti-PD-1 monoclonal antibody, IV infusion
Drug: Cisplatin (or carboplatin)
IV infusion
Biological: Bevacizumab
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 6 months
ORR is defined as the percentage of the participants in the mITT population who have a Complete Response or a Partial Response. The ORR will be assessed by a blind independent central reviewer per RECIST 1.1 and iRECIST.
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
1-year Overall Survival (OS)
Time Frame: 1 year
1 year
Median Progression-free Survival (PFS)
Time Frame: 1 year
1 year
1-year Progression-free Survival (PFS)
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biocad

Investigators

  • Study Director: Roman A Ivanov, PhD, Vice President R&D, JSC BIOCAD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 25, 2018

Primary Completion (Anticipated)

July 7, 2020

Study Completion (Anticipated)

July 7, 2020

Study Registration Dates

First Submitted

April 10, 2019

First Submitted That Met QC Criteria

April 10, 2019

First Posted (Actual)

April 11, 2019

Study Record Updates

Last Update Posted (Actual)

May 9, 2019

Last Update Submitted That Met QC Criteria

May 8, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCD-100-4/CAESURA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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