Clinical trial NCT02467907: Safety and Efficacy of Bevacizumab in Combination With Carboplatin and Paclitaxel for Metastatic, Recurrent or Persistent Cervical Cancer
Official title: A Multicenter Open-Label Single-Arm Phase II Study Evaluating the Safety and Efficacy of Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Metastatic, Recurrent or Persistent Cervical Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-06-10
Enrollment: 152
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Known hypersensitivity to bevacizumab or any of its excipients, Chinese hamster ovary cell products or other recombinant human or humanized antibodies to any planned chemotherapy
* Active GI bleeding or ulcer
* Uncontrolled hypertension
* Clinically significant active cardiovascular disease
* National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, Grade greater than or equal to (\>=) 2 peripheral vascular disease

Primary outcomes:
measure: 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
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with GI-Vaginal Fistula Events by Grade According to NCI-CTCAE Version 4.0
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with GU Fistula Events by Grade According to NCI-CTCAE Version 4.0
timeFrame: Baseline up to 24 months
Secondary outcomes:
measure: Time to First GI Perforation/Fistula
timeFrame: Baseline up to 24 months
measure: Time to First GI-Vaginal Fistula
timeFrame: Baseline up to 24 months
measure: Time to First GU Fistula
timeFrame: Baseline up to 24 months
measure: Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Bevacizumab During the Treatment Period
timeFrame: Baseline up to 24 months
measure: Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Carboplatin During the Treatment Period
timeFrame: Baseline up to 24 months
measure: Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Paclitaxel During the Treatment Period
timeFrame: Baseline up to 24 months
measure: Duration of Treatment for Bevacizumab
timeFrame: Baseline up to 24 months
measure: Duration of Treatment for Carboplatin
timeFrame: Baseline up to 24 months
measure: Duration of Treatment for Paclitaxel
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with Serious Adverse Events (SAEs)
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with Adverse Events of Special Interest (AESIs)
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with AEs Leading to Treatment Interruption or Permanent discontinuation
timeFrame: Baseline up to 24 months
measure: Percentage of Deaths Causally Related to Treatment
timeFrame: Baseline up to 24 months
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria for Solid Tumors (RECIST) Version 1.1
timeFrame: Baseline up to 24 months
measure: Overall Survival (OS)
timeFrame: Baseline up to 24 months
measure: Percentage of Participants with a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1
timeFrame: Baseline up to 24 months
Other outcomes:
Locations:
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas - UFMG
state: MG
city: Belem
country: Brazil
facility: Oncologica Brasil S/S LTDA - EPP
state: PA
city: Rio De Janerio
country: Brazil
facility: Instituto Nacional de Cancer - INCa; Pesquisa Clinica
state: RJ
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Plovdiv
country: Bulgaria
facility: Complex Oncological Center - Plovdiv, EOOD
city: Sofia
country: Bulgaria
facility: MHAT Nadezhda
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Pereira
country: Colombia
facility: Oncólogos de Occidente
city: San Jose
country: Costa Rica
facility: Clinica CIMCA
city: Caen
country: France
facility: Centre Francois Baclesse; Urologie Gynecologie
city: Villejuif
country: France
facility: Institut Gustave Roussy; Oncologie Medicale
city: Athens
country: Greece
facility: Alexandras General Hospital of Athens; Oncology Department
city: Athens
country: Greece
facility: IASO
city: Napoli
country: Italy
facility: Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica
state: Campania
city: Roma
country: Italy
facility: Universita' Cattolica Del Sacro Cuore; Reparto Ginecologia Oncologica
state: Lazio
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
state: Lombardia
city: Mexico
country: Mexico
facility: Consultorio de Medicina Especializada
state: Mexico CITY (federal District)
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Cancerologia; Oncology
city: Toluca
country: Mexico
facility: Centro Oncologico Estatal ISSEMYM
city: Panama
country: Panama
facility: Centro Oncológico de Panamá
city: Panama
country: Panama
facility: Centro Hemato Oncologico Panama
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologi
city: Krakow
country: Poland
facility: Centrum Onkologii Instytut im. M.Sklodowskiej-Curie; Klinika Ginekologii Onkologicznej
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut M.Sklodowskiej-Curie; Klinika Ginekologii Onkologicznej
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Craiova
country: Romania
facility: Centrul de Oncologie Sfantul Nectarie
city: Iasi
country: Romania
facility: Regional Institute of Oncology Iasi
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
city: Saint-Petersburg
country: Russian Federation
facility: St. Petersburg Oncology & Gynecology; City Clinical Oncology Dispensary
city: Belgrade
country: Serbia
facility: Institute for Onc/Rad Serbia
city: Johannesberg
country: South Africa
facility: Wits Clinical Research
city: Pretoria
country: South Africa
facility: University of Pretoria; Department of Medical Oncology
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals; Oncologia
city: Madrid
country: Spain
facility: Centro Oncologico MD Anderson International Espana
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia; Oncologia Medica
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Oncologia
city: Ankara
country: Turkey
facility: Ankara Baskent University Medicine Faculty; Gynaecology
city: Istanbul
country: Turkey
facility: Istanbul Uni of Medicine Faculty; Oncology Dept
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.