Safety and Efficacy of Bevacizumab in Combination With Carboplatin and Paclitaxel for Metastatic, Recurrent or Persistent Cervical Cancer

NCT02467907 | Completed Phase 2

• 2 other identifiers: MO295942014-005491-28
• Study Type: interventional
• Target: 152
• Locations: 17 countries
• Sites: 41

Brief Summary

This study is to assess safety as defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, GI-vaginal fistula and genitourinary (GU) fistula in participants treated with bevacizumab 15 milligrams per kilogram (mg/kg) in combination with paclitaxel and carboplatin, all repeated every 3 weeks, for recurrent, persistent or metastatic cervical cancer. In addition, this study will include evaluation of the overall safety profile of bevacizumab in combination with paclitaxel and carboplatin in this setting, assessment of GI perforation/fistula, GI-vaginal fistula and GU fistula events over time, and evaluation of efficacy.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with GI Perforation/Fistula Events by Grade According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0

  Baseline up to 24 months

• Percentage of Participants with GI-Vaginal Fistula Events by Grade According to NCI-CTCAE Version 4.0

  Baseline up to 24 months

• Percentage of Participants with GU Fistula Events by Grade According to NCI-CTCAE Version 4.0

  Baseline up to 24 months

Secondary Outcomes (17)

• Time to First GI Perforation/Fistula

  Baseline up to 24 months

• Time to First GI-Vaginal Fistula

  Baseline up to 24 months

• Time to First GU Fistula

  Baseline up to 24 months

• Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Bevacizumab During the Treatment Period

  Baseline up to 24 months

• Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Carboplatin During the Treatment Period

  Baseline up to 24 months

Study Arms (1)

Bevacizumab in Combination with Carboplatin and Paclitaxel

EXPERIMENTAL

Administration of bevacizumab, carboplatin and paclitaxel once every 3 weeks, for at least 6 cycles, until disease progression (as assessed by the investigator), unacceptable toxicity, physician or participant decision or withdrawal of consent. If either chemotherapy or bevacizumab is discontinued, the participant may continue to receive the other ongoing therapy.

Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Bevacizumab DRUG

Intravenous (i.v.) administration of 15 mg/kg bevacizumab once every 3 weeks

Also known as: Avastin, RO4876646

Bevacizumab in Combination with Carboplatin and Paclitaxel

Carboplatin DRUG

Administration of carboplatin at 5 milligrams per milliliter\*minute (mg/mL\*min) on Day 1 every 3 weeks for at least 6 cycles

Bevacizumab in Combination with Carboplatin and Paclitaxel

Paclitaxel DRUG

Administration of paclitaxel at a dose of 175 milligrams per square meter (mg/m\^2) on Day 1 every 3 weeks for at least 6 cycles

Bevacizumab in Combination with Carboplatin and Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy greater than or equal to (\>=3) months
• For women who are not postmenopausal or surgically sterile, agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 6 months after the last dose of study drug
• Distant metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy
• Either measurable or non-measurable disease. If disease is non-measurable or limited to the radiation field, a biopsy or fine-needle aspiration is required to confirm malignancy
• Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care
• Adequate hematological, renal and hepatic function
• Normal blood coagulation parameters
• Recovered (to Grade less than or equal to \[\<=\] 1) from the effects of prior surgery, radiation therapy or chemoradiotherapy

You may not qualify if:

• Pregnant or lactating
• History of other malignancy within 5 years before screening, except for non-melanoma skin carcinoma
• Ongoing disease involving the bladder or rectum at screening/baseline. In participants with pelvic disease, absence of tumor in the bladder or rectal mucosa must be demonstrated by magnetic resonance imaging (MRI) (preferred method, or endoscopy/cystoscopy if MRI is not easily accessible) within 28 days before enrolment
• Evidence of abdominal free air
• Bilateral hydronephrosis
• Untreated central nervous system (CNS) metastases
• Prior chemotherapy for recurrent, persistent or metastatic cervical cancer. Prior adjuvant or neoadjuvant chemotherapy for Stage I-IVA disease (i.e. for non-metastatic disease) is permitted if completed greater than (\>) 6 months before first study dose
• Prior chemoradiation within the 3 months preceding first study dose
• Prior radiotherapy delivered using cobalt
• Prior or current bevacizumab or other anti-angiogenic treatment
• Requirement for treatment with any medicinal product that contraindicates the use of any of the study drugs, may interfere with the planned treatment, affects participant compliance or puts the participant at high risk for treatment-related complications
• Treatment with another investigational agent within 28 days or 2 investigational agent half-lives before first study dose
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before the first dose of bevacizumab or anticipation of the need for major surgery during the course of study treatment
• Minor surgical procedure within 2 days before the first dose of study drug
• Any prior history of fistula or GI perforation

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (43)

Centro Oncologico Riojano Integral (CORI)

La Rioja, F5300COE, Argentina

Location

Hospital das Clinicas - UFMG

Belo Horizonte, Minas Gerais, 31270-901, Brazil

Location

Oncologica Brasil S/S LTDA - EPP

Belém, Pará, 66053-000, Brazil

Location

Instituto Nacional de Cancer - INCa; Pesquisa Clinica

Rio de Janerio, Rio de Janeiro, 20560-120, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Complex Oncological Center - Plovdiv, EOOD

Plovdiv, 4004, Bulgaria

Location

MHAT Nadezhda

Sofia, 1330, Bulgaria

Location

Oncomedica S.A.

Montería, 230002, Colombia

Location

Oncólogos de Occidente

Pereira, 600004, Colombia

Location

Clinica CIMCA

San José, 10103, Costa Rica

Location

Centre Francois Baclesse; Urologie Gynecologie

Caen, 14076, France

Location

Institut Gustave Roussy; Oncologie Medicale

Villejuif, 94800, France

Location

Alexandras General Hospital of Athens; Oncology Department

Athens, 115280, Greece

Location

IASO

Athens, 151 23, Greece

Location

Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica

Napoli, Campania, 80131, Italy

Location

Universita' Cattolica Del Sacro Cuore; Reparto Ginecologia Oncologica

Rome, Lazio, 00168, Italy

Location

Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica

Milan, Lombardy, 20133, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

Milan, Lombardy, 20141, Italy

Location

Consultorio de Medicina Especializada

México, Mexico CITY (federal District), 03100, Mexico

Location

Instituto Nacional de Cancerologia; Oncology

Distrito Federal, 14080, Mexico

Location

Centro Oncologico Estatal ISSEMYM

Toluca, 50180, Mexico

Location

Centro Oncológico de Panamá

Panama City, 0801, Panama

Location

Centro Hemato Oncologico Panama

Panama City, 0832, Panama

Location

Bialostockie Centrum Onkologi

Bialystok, 15-027, Poland

Location

Centrum Onkologii Instytut im. M.Sklodowskiej-Curie; Klinika Ginekologii Onkologicznej

Krakow, 31-115, Poland

Location

Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie

Poznan, 61-866, Poland

Location

Centrum Onkologii - Instytut M.Sklodowskiej-Curie; Klinika Ginekologii Onkologicznej

Warsaw, 02-781, Poland

Location

IPO do Porto; Servico de Oncologia Medica

Porto, 4200-072, Portugal

Location

Centrul de Oncologie Sfantul Nectarie

Craiova, 200347, Romania

Location

Regional Institute of Oncology Iasi

Iași, 700483, Romania

Location

Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy

Moscow, 115478, Russia

Location

St. Petersburg Oncology & Gynecology; City Clinical Oncology Dispensary

Saint Petersburg, 197022, Russia

Location

Institute for Onc/Rad Serbia

Belgrade, 11000, Serbia

Location

Wits Clinical Research

Johannesberg, 2013, South Africa

Location

University of Pretoria; Department of Medical Oncology

Pretoria, 0002, South Africa

Location

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Hospital Duran i Reynals; Oncologia

Barcelona, 08907, Spain

Location

Centro Oncologico MD Anderson International Espana

Madrid, 28033, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, 28046, Spain

Location

Instituto Valenciano Oncologia; Oncologia Medica

Valencia, 46009, Spain

Location

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, 46026, Spain

Location

Ankara Baskent University Medicine Faculty; Gynaecology

Ankara, 06500, Turkey (Türkiye)

Location

Istanbul Uni of Medicine Faculty; Oncology Dept

Istanbul, 34390, Turkey (Türkiye)

Location

Related Publications (1)

• Redondo A, Colombo N, McCormack M, Dreosti L, Nogueira-Rodrigues A, Scambia G, Lorusso D, Joly F, Schenker M, Ruff P, Estevez-Diz M, Irahara N, Donica M, Gonzalez-Martin A. Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer. Gynecol Oncol. 2020 Oct;159(1):142-149. doi: 10.1016/j.ygyno.2020.07.026. Epub 2020 Aug 4.

  PMID: 32763109 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Bevacizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: June 10, 2015
• Study Start: July 28, 2015
• Primary Completion: December 31, 2018
• Study Completion: January 15, 2019
• Last Updated: June 3, 2019

Record last verified: 2019-05

Locations

AR (1); PA (2); RO (2); ES (6); BR (4); PL (4); GR (2); SE (1); ZA (2); FR (2); BU (2); PT (1); CO (1); RU (2); ME (3); TU (2); IT (4)