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

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02467907
• Other study ID #: MO29594
• Secondary ID: 2014-005491-28
• Status: Completed
• Phase: Phase 2
• Start date: July 28, 2015
• Est. completion date: January 15, 2019

Study information

• Verified date: May 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: January 15, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• Bevacizumab
Intravenous (i.v.) administration of 15 mg/kg bevacizumab once every 3 weeks
• Carboplatin
Administration of carboplatin at 5 milligrams per milliliter*minute (mg/mL*min) on Day 1 every 3 weeks for at least 6 cycles
• Paclitaxel
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

Locations

Country	Name	City	State
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Brazil	Oncologica Brasil S/S LTDA - EPP	Belem	PA
Brazil	Hospital das Clinicas - UFMG	Belo Horizonte	MG
Brazil	Instituto Nacional de Cancer - INCa; Pesquisa Clinica	Rio De Janerio	RJ
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Bulgaria	Complex Oncological Center - Plovdiv, EOOD	Plovdiv
Bulgaria	MHAT Nadezhda	Sofia
Colombia	Oncomedica S.A.	Monteria
Colombia	Oncólogos de Occidente	Pereira
Costa Rica	Clinica CIMCA	San Jose
France	Centre Francois Baclesse; Urologie Gynecologie	Caen
France	Institut Gustave Roussy; Oncologie Medicale	Villejuif
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	IASO	Athens
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia
Italy	Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica	Milano	Lombardia
Italy	Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica	Napoli	Campania
Italy	Universita' Cattolica Del Sacro Cuore; Reparto Ginecologia Oncologica	Roma	Lazio
Mexico	Instituto Nacional de Cancerologia; Oncology	Distrito Federal
Mexico	Consultorio de Medicina Especializada	Mexico	Mexico CITY (federal District)
Mexico	Centro Oncologico Estatal ISSEMYM	Toluca
Panama	Centro Hemato Oncologico Panama	Panama
Panama	Centro Oncológico de Panamá	Panama
Poland	Bialostockie Centrum Onkologi	Bialystok
Poland	Centrum Onkologii Instytut im. M.Sklodowskiej-Curie; Klinika Ginekologii Onkologicznej	Krakow
Poland	Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie	Poznan
Poland	Centrum Onkologii - Instytut M.Sklodowskiej-Curie; Klinika Ginekologii Onkologicznej	Warszawa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Centrul de Oncologie Sfantul Nectarie	Craiova
Romania	Regional Institute of Oncology Iasi	Iasi
Russian Federation	Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy	Moscow
Russian Federation	St. Petersburg Oncology & Gynecology; City Clinical Oncology Dispensary	Saint-Petersburg
Serbia	Institute for Onc/Rad Serbia	Belgrade
South Africa	Wits Clinical Research	Johannesberg
South Africa	University of Pretoria; Department of Medical Oncology	Pretoria
Spain	Hospital Duran i Reynals; Oncologia	Barcelona
Spain	Centro Oncologico MD Anderson International Espana	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Turkey	Ankara Baskent University Medicine Faculty; Gynaecology	Ankara
Turkey	Istanbul Uni of Medicine Faculty; Oncology Dept	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Brazil,  Bulgaria,  Colombia,  Costa Rica,  France,  Greece,  Italy,  Mexico,  Panama,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of Participants with GI-Vaginal Fistula Events by Grade According to NCI-CTCAE Version 4.0		Baseline up to 24 months
Primary	Percentage of Participants with GU Fistula Events by Grade According to NCI-CTCAE Version 4.0		Baseline up to 24 months
Secondary	Time to First GI Perforation/Fistula		Baseline up to 24 months
Secondary	Time to First GI-Vaginal Fistula		Baseline up to 24 months
Secondary	Time to First GU Fistula		Baseline up to 24 months
Secondary	Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Bevacizumab During the Treatment Period		Baseline up to 24 months
Secondary	Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Carboplatin During the Treatment Period		Baseline up to 24 months
Secondary	Dose Intensity (Ratio of Actual Dose Administered Versus Intended Dose) for Paclitaxel During the Treatment Period		Baseline up to 24 months
Secondary	Duration of Treatment for Bevacizumab		Baseline up to 24 months
Secondary	Duration of Treatment for Carboplatin		Baseline up to 24 months
Secondary	Duration of Treatment for Paclitaxel		Baseline up to 24 months
Secondary	Percentage of Participants with Adverse Events (AEs)		Baseline up to 24 months
Secondary	Percentage of Participants with Serious Adverse Events (SAEs)		Baseline up to 24 months
Secondary	Percentage of Participants with Adverse Events of Special Interest (AESIs)		Baseline up to 24 months
Secondary	Percentage of Participants with AEs Leading to Treatment Interruption or Permanent discontinuation		Baseline up to 24 months
Secondary	Percentage of Deaths Causally Related to Treatment		Baseline up to 24 months
Secondary	Progression-Free Survival (PFS) According to Response Evaluation Criteria for Solid Tumors (RECIST) Version 1.1		Baseline up to 24 months
Secondary	Overall Survival (OS)		Baseline up to 24 months
Secondary	Percentage of Participants with a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1		Baseline up to 24 months