Low Dose Cyclophosphamide +/-- Nintedanib in Advanced Ovarian Cancer
METRO-BIBF
Phase II, Randomised, Placebo Controlled, Multicentre, Feasibility Study of Low Dose (Metronomic) Cyclophosphamide With and Without Nintedanib (BIBF 1120) in Advanced Ovarian Cancer
2 other identifiers
interventional
117
1 country
16
Brief Summary
The primary objective is to explore the efficacy and safety of an all oral combination of BIBF 1120 (an inhibitor of angiogenic signalling) and metronomic cyclophosphamide in patients with multiply-relapsed advanced ovarian cancer, who have completed a minimum of two lines of previous chemotherapy and who for any reason are not suitable for further 'standard' intravenous chemotherapy treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 ovarian-cancer
Started Aug 2014
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 25, 2011
CompletedFirst Posted
Study publicly available on registry
June 4, 2012
CompletedStudy Start
First participant enrolled
August 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 11, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 11, 2018
CompletedMay 29, 2019
October 1, 2018
3.4 years
November 25, 2011
May 24, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival
To be measured in days, from the date of randomisation to the date of death.
After follow-up is complete (year 3-4 of the trial)
Secondary Outcomes (3)
Quality of life and qualitative health data
After follow-up is complete (year 3-4 of the trial)
Adverse events for all patients
After follow-up is complete (year 3-4 of the trial)
Progression free survival
After follow-up is complete (year 3-4 of the trial)
Study Arms (2)
Cyclophosphamide and BIBF-1120
EXPERIMENTALPatients will receive oral BIBF 1120 (200mg bd) and cyclophosphamide (100mg) on a daily basis until disease progression or unacceptable toxicity.
Cyclophosphamide and placebo
PLACEBO COMPARATORPatients will receive oral BIBF 1120 (200mg bd) and placebo capsules on a daily basis until disease progression or unacceptable toxicity.
Interventions
Patients will receive either cyclophosphamide (100mg)and oral BIBF 1120 (200mg bd) or cyclophosphamide (100mg) and placebo.
Eligibility Criteria
You may qualify if:
- Female subjects, ≥18 years, histologically proven recurrent advanced epithelial ovarian, fallopian tube or primary peritoneal carcinomas
- Have either undergone a hysterectomy or bilateral oophorectomy/salpingectomy and/or have been postmenopausal for 24 consecutive months (i.e. who have not had menses at any time in the preceding 24 consecutive months without an alternative medical cause)
- Performance status 0-2
- Adequate organ function
- Life expectancy \>6 weeks
- Has received 2 or more lines of chemotherapy for ovarian cancer and patient is platinum resistant or platinum intolerant or not suitable for any further standard intravenous chemotherapy
- No previous oral cyclophosphamide, nintedanib, or other tyrosine kinase inhibitors such as cediranib but patients can have received anti-VEGF therapies such as bevacizumab as they will be stratified for this
- Able to give written informed consent and to complete QoL
You may not qualify if:
- Carcinosarcoma or malignant tumour of non-epithelial origin (e.g. germ cell tumour, sex cord-stromal tumour) of the ovary, fallopian tube or peritoneum
- Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture
- Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other GI disorders or abnormalities that would interfere with drug absorption or inability to take oral medication
- Active brain metastases (i.e. symptoms deteriorating, changing condition in \< 4 weeks) or leptomeningeal disease. Trial entry is allowed if the brain metastases are stable (asymptomatic or condition stable for \> 4 weeks).
- Dexamethasone for brain metastases is allowed if administered as stable dose for \> 4 weeks before randomisation (if \< 4 weeks then the patient is not eligible)
- Clinically relevant therapy-related toxicity from previous chemotherapy and radiotherapy
- History of major thromboembolic event within the last 6 months, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation (\>3 months if on warfarin, PT / INR needs to be monitored regularly as per table 8.1 in protocol)
- Known inherited or acquired bleeding disorder
- Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within the past 6 months, congestive heart failure \> NYHA II, severe peripheral vascular disease, significantly relevant pericardial effusion
- History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months
- Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vessels
- Laboratory values indicating an increased risk for adverse events:
- calculated GFR \< 45 ml/min. Sites can use any calculation method according to local practice.
- absolute neutrophil count (ANC) \< 1.5x109/L
- platelets \< 100 x109/L
- +23 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Boehringer Ingelheimcollaborator
Study Sites (16)
Kent Oncology Centre
Maidstone, Kent, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom
Velindre Hospital
Cardiff, Wales, United Kingdom
Royal United Hospital
Bath, United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom
Royal Derby Hospital
Derby, United Kingdom
Royal Surrey County Hospital
Guildford, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Clatterbridge Centre for Oncology
Liverpool, United Kingdom
Mount Vernon Hospital
London, United Kingdom
Royal Marsden Hospital
London, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
University College London Hospital (UCLH)
London, United Kingdom
Christie Hospital
Manchester, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Wexham Park Hospital
Slough, United Kingdom
Related Publications (2)
Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
PMID: 37185961DERIVEDHall MR, Dehbi HM, Banerjee S, Lord R, Clamp A, Ledermann JA, Nicum S, Lilleywhite R, Bowen R, Michael A, Feeney A, Glasspool R, Hackshaw A, Rustin G. A phase II randomised, placebo-controlled trial of low dose (metronomic) cyclophosphamide and nintedanib (BIBF1120) in advanced ovarian, fallopian tube or primary peritoneal cancer. Gynecol Oncol. 2020 Dec;159(3):692-698. doi: 10.1016/j.ygyno.2020.09.048. Epub 2020 Oct 16.
PMID: 33077258DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dr Marcia Hall
Mount Vernon Cancer Centre
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 25, 2011
First Posted
June 4, 2012
Study Start
August 1, 2014
Primary Completion
January 11, 2018
Study Completion
January 11, 2018
Last Updated
May 29, 2019
Record last verified: 2018-10
Data Sharing
- IPD Sharing
- Will not share