AzTrials
AzTrials

Ovarian CancerPhase 2METRO-BIBFNCT01610869

Low Dose Cyclophosphamide +/-- Nintedanib in Advanced Ovarian Cancer

A Phase 2 study testing BIBF 1120 in people with Ovarian Cancer and Fallopian Tube Cancer, run by University College, London at 16 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer, Fallopian Tube Cancer
What is being tested?
BIBF 1120
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
117 participants
Where
16 sitesUnited Kingdom
Study dates
Aug 2014to 11 Jan 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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
  • Measurable lesions according to RECIST 1.1 criteria or serum CA125 levels for evaluation by GCIG CA125 criteria are welcomed but not a prerequisite for inclusion as response will only be assessed for those with evaluable disease
  • Able to give written informed consent and to complete QoL

Who cannot join

  • 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
Show all 38Show fewer
  • 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
  • haemoglobin < 90 g/L
  • proteinuria CTCAE 2 or greater
  • total bilirubin > x 2 ULN
  • ALT and/or AST > 1.5 x ULN
  • unless liver metastases present when ALT or AST > 2.5 ULN
  • International normalized ratio (INR) > 2 or activated partial thromboplastin time (APTT) >1.5 x ULN in the absence of therapeutic anticoagulation. INR > 4 or APTT > 2.5 x ULN in presence of therapeutic anticoagulation
  • Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal or antiviral therapy), including hepatitis B and/or C infection, HIV- infection
  • Poorly controlled diabetes mellitus or patient on sulphonylurea-type hypoglycaemics (e.g. gliclazide) as main diabetic control (as contraindicated with cyclophosphamide)
  • Previous breast cancer patients are permitted only if diagnosis and any chemotherapy treatment for this was > 5 years previously and there is no evidence of metastatic breast cancer at trial entry (Please contact UCL CTC / CI if patient still on hormone treatment for breast cancer).
  • Other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included:
  • non-melanoma skin cancer (if adequately treated)
  • cervical carcinoma in situ (if adequately treated)
  • prior or synchronous endometrial cancer (if adequately treated), provided all of the following criteria are met: G1 or G2, no LVSI and FIGO (2010) stage IA only
  • Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease or a laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
  • Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule e.g. active alcohol or drug abuse
  • Any contraindications for therapy with cyclophosphamide, e.g. a history of severe hypersensitivity reactions to listed excipients for cyclophosphamide treatment with other investigational drugs
  • Patients should not commence trial treatment within 6 weeks of any major surgical procedure
  • Participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial
  • Chemotherapy, including immunotherapy or monoclonal antibody treatment (VEGF) within 4 weeks of starting study treatment
  • Hormone treatment for ovarian cancer within 2 weeks of starting study treatment (ongoing HRT is allowable)
  • Any previous tyrosine kinase inhibitor treatment that has predominantly anti-angiogenic action
  • Radiotherapy within 3 months not allowed except when given for symptom control >28d previously. All patients receiving any radiotherapy will require evidence of recurrent ovarian cancer outside the irradiated field either on imaging or via rising CA125
  • Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients of nintedanib

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United Kingdom16 sites

  • Royal United Hospital

    Bath

  • Addenbrookes Hospital

    Cambridge

  • Velindre Hospital

    Cardiff, Wales

  • Royal Derby Hospital

    Derby

  • Beatson West of Scotland Cancer Centre

    Glasgow, Scotland

  • Royal Surrey County Hospital

    Guildford

  • St James's University Hospital

    Leeds

  • Clatterbridge Centre for Oncology

    Liverpool

  • Mount Vernon Hospital

    London

  • Royal Marsden Hospital

    London

  • St Bartholomew's Hospital

    London

  • University College London Hospital (UCLH)

    London

  • Kent Oncology Centre

    Maidstone, Kent

  • Christie Hospital

    Manchester

  • Churchill Hospital

    Oxford

  • Wexham Park Hospital

    Slough

Other trials in United Kingdom

About this study

Official title: Phase II, Randomised, Placebo Controlled, Multicentre, Feasibility Study of Low Dose (Metronomic) Cyclophosphamide With and Without Nintedanib (BIBF 1120) in Advanced Ovarian Cancer

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.

Read the detailed description

A randomised placebo controlled double blind multi-centre phase II trial: BIBF 1120 200mg bd plus 100mg daily of oral cyclophosphamide (experimental arm) or oral cyclophosphamide 100mg daily plus placebo (control arm). Patients will receive oral BIBF 1120 and cyclophosphamide or cyclophosphamide and placebo continuously until disease progression or unacceptable toxicity.

Being tested
BIBF 1120
Keywords
Recurrence, Ovarian Neoplasms, Ovarian Diseases, Fallopian Tube Neoplasms, Neoplasms, Carcinoma, Neoplasms by site
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms, Recurrence, Ovarian Diseases, Neoplasms, Carcinoma, Neoplasms by Site

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BIBF 1120Drug

    Also called BIBF 1120 brand name: Nintedanib.

    Patients will receive either cyclophosphamide (100mg)and oral BIBF 1120 (200mg bd) or cyclophosphamide (100mg) and placebo.

Study groups in NCT01610869
Study groupRoleWhat they receive
Cyclophosphamide and BIBF-1120ExperimentalPatients will receive oral BIBF 1120 (200mg bd) and cyclophosphamide (100mg) on a daily basis until disease progression or unacceptable toxicity.
Receives: Drug: BIBF 1120
Cyclophosphamide and placeboPlacebo comparatorPatients will receive oral BIBF 1120 (200mg bd) and placebo capsules on a daily basis until disease progression or unacceptable toxicity.
Receives: Drug: BIBF 1120

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    To be measured in days, from the date of randomisation to the date of death.

    Measured: After follow-up is complete (year 3-4 of the trial)

Secondary outcomes (3)

  1. Quality of life and qualitative health data

    Health questionnaires which record qualitative health data on the patient perspective of their illness and treatment. This will be measured on a 6 weekly basis, from baseline to the end of treatment.

    Measured: After follow-up is complete (year 3-4 of the trial)

  2. Adverse events for all patients

    Adverse events will be collected for patients in both groups during treatment and the groups compared during analysis. This will be measured on a 6 weekly basis, from baseline to the end of treatment. The first 12 patients will be assessed on a 3 weekly basis, from baseline to end of treatment.

    Measured: After follow-up is complete (year 3-4 of the trial)

  3. Progression free survival

    Progression free survival will be determined by measurement of tumour size using RECIST 1.1 at progression or by a rise in CA-125 tumour marker. Measured from the date of randomisation until date of confirmed disease progression. Tumour assessment carried out on 3 monthly basis, CA-125 carried out on 6 weekly basis.

    Measured: After follow-up is complete (year 3-4 of the trial)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2012 (estimated)
  2. Study startAug 2014
  3. Primary completion11 Jan 2018
  4. Study completion11 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01610869
Sponsor's protocol ID
UCL/10/0470
Other IDs
2011-005814-12
Acronym
METRO-BIBF
Status last verified
Oct 2018
First submitted
25 Nov 2011
Last updated
29 May 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 37185961

  • Hall 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.

    PubMed 33077258

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BIBF 1120 in people with Ovarian Cancer and Fallopian Tube Cancer, run by University College, London at 16 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: After follow-up is complete (year 3-4 of the trial)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01610869, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in