A MULTICENTRE 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

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2014-005491-28-PL
• Date of registration: 08/07/2015
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A MULTICENTRE 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
• Scientific title: A MULTICENTRE 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
• Date of first enrolment: 25/07/2015
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005491-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Bulgaria, Colombia, Costa Rica, Ecuador, France, Greece, Guatemala, Italy, Mexico, Panama, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Turkey, Venezuela, Bolivarian Republic of

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Female aged >=18 years
- Eastern Cooperative Oncology Group performance status score 0 or 1
- Life expectancy >=3 months
- Able (in the investigator’s judgement) to comply with the study protocol.
- Female patients of childbearing potential must agree with the required contraceptive methods as defined per protocol
- 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 nonmeasurable 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 haematological, renal and hepatic function as defined in the protocol
- Normal blood coagulation parameters
- Recovered (to grade <=1) from the effects of prior surgery, radiation therapy or chemoradiotherapy. At least 6 weeks must have elapsed between the last dose of palliative radiation and the first dose of bevacizumab.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
- Pregnant or lactating women
- 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
- Evidence of abdominal free air
- Bilateral hydronephrosis, unless it can be alleviated by ureteral stent(s) or percutaneous drainage
- Untreated central nervous system (CNS) metastases. Patients with adequately treated brain metastases/spinal cord compression that is stable without anti-cancer steroid treatment for >4 weeks are eligible.
- Prior chemotherapy for recurrent, persistent or metastatic cervical cancer (prior adjuvant or neoadjuvant chemotherapy is permitted if completed >6 months before first study dose)
- Prior chemoradiation within the 3 months preceding first study dose
- Prior radiotherapy delivered using cobalt
- Serious active infection requiring IV antibiotics at screening/baseline
- Known active human immunodeficiency virus infection that is not adequately controlled
- 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 patient compliance or puts the patient at high risk for treatment-related complications
- Treatment with another investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) before first study dose
- Current or recent (within 10 days before the first dose of study drug) chronic daily treatment with aspirin (>325 milligrams [mg]/day), clopidogrel (>75 mg/day), or current or recent (within 10 days before first dose of bevacizumab) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes.
- 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
- Clinical signs or symptoms of GI obstruction requiring parenteral hydration and/or nutrition
- Intra-abdominal abscess within 6 months before the first dose of bevacizumab
- Active GI bleeding or ulcer
- History of Crohn’s disease or inflammatory bowel disease
- Prior bowel resection <=6 weeks preceding first study dose
- History of diverticulitis requiring medical intervention
- National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.0) grade >=2 enteritis
- History of myocardial infarction, unstable angina, subarachnoid haemorrhage, stroke or transient ischaemic attack within 6 months before first dose of study drug
- Uncontrolled hypertension (current systolic blood pressure [BP] >150 millimetre of mercury (mmHg) and/or diastolic BP >100 mmHg or history of hypertensive crisis or hypertensive encephalopathy)
- Clinically significant active cardiovascular disease
- Serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate
- NCI CTCAE (version 4.0) grade >=2 peripheral vascular disease
- History or evidence upon physical/neurological examination of CNS disease unrelated to cancer unless adequately t

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Metastatic, Recurrent or Persistent Cervical Cancer
MedDRA version: 19.1 Level: LLT Classification code 10008236 Term: Cervical cancer stage IV System Organ Class: 100000004864

Intervention(s)

Trade Name: Avastin
Product Name: Bevacizumab
Product Code: RO4876646/F02
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Current Sponsor code: RO4876646/F02
Other descriptive name: rhuMAb VEGF, anti-VEGF
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 25-

Trade Name: Carboplatin 10 mg/ml Intravenous Infusion
Product Name: Carboplatin
Product Code: RO484-3791
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Current Sponsor code: RO484-3791
Other descriptive name: CARBOPLATIN
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 150-

Trade Name: Carboplatin 10 mg/ml Intravenous Infusion
Product Name: Carboplatin
Product Code: RO484-3791
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Current Sponsor code: RO484-3791
Other descriptive name: CARBOPLATIN
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 450-

Trade Name: Carboplatin 10 mg/ml concentrate for solution for infusion.
Product Name: Carboplatin
Product Code: RO484-3791
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Current Sponsor code: RO484-3791
Other descriptive name: CARBOPLATIN
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 150-

Trade Name: Carboplatin 10 mg/ml concentrate for solution for infusion.
Product Name: Carboplatin
Product Code: RO484-3791
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Current Sponsor code: RO484-3791
Other descript

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 42 months

Secondary Objective: • To define the safety and tolerability of bevacizumab in combination with carboplatin and paclitaxel therapy for recurrent, persistent or metastatic cervical cancer by describing the nature, frequency, severity and duration of adverse events (AEs)
• To evaluate the incidence of GI perforation/fistula, GI-vaginal fistula and GU fistula events over time
• To evaluate the efficacy of bevacizumab in combination with carboplatin and paclitaxel therapy for metastatic, recurrent or persistent cervical cancer, as measured by:
?-Progression-free survival determined by the investigator
?-Overall survival
?-Overall response rate (investigator-assessed).

Main Objective: To determine the safety of bevacizumab in combination with carboplatin and paclitaxel therapy for metastatic, recurrent or persistent cervical cancer, as defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, GI-vaginal fistula and genitourinary (GU) fistula events

Primary end point(s): Incidence of GI perforation/fistula, GI-vaginal fistula and GU fistula (separately; all grades, grade 3/4 and grade 5)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For all above listed (1-9.) secondary end points: Up to 42 months

Secondary end point(s): 1) Time to first GI perforation/fistula, GI-vaginal fistula and GU fistula
2) Overall survival
3) Overall response rate
4) Progression-free survival (after first study dose bevacizumab or chemotherapy)
5) Treatment exposure (dose and duration of treatment for each drug)
6) Incidence of AEs, Serious AEs, and AEs of special interest for bevacizumab
7) Changes in physical findings and clinical laboratory results during and following bevacizumab administration
8) AEs leading to treatment interruption or permanent discontinuation of any study drug
9) Cause of death

Secondary ID(s)

MO29594

2014-005491-28-ES

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 24/06/2015
Contact:

Results

• Results available: Yes
• Date Posted: 27/12/2019
• Date Completed: 31/12/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-005491-28/results