Low Dose Cyclophosphamide +/-- Nintedanib in Advanced Ovarian Cancer (METRO-BIBF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University College, London
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01610869
First received: November 25, 2011
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Drug: BIBF 1120
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Overall survival [ Time Frame: After follow-up is complete (year 3-4 of the trial) ] [ Designated as safety issue: No ]
    To be measured in days, from the date of randomisation to the date of death.


Secondary Outcome Measures:
  • Quality of life [ Time Frame: After follow-up is complete (year 3-4 of the trial) ] [ Designated as safety issue: No ]
    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.

  • Adverse events for all patients [ Time Frame: After follow-up is complete (year 3-4 of the trial) ] [ Designated as safety issue: Yes ]
    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.

  • Progression free survival [ Time Frame: After follow-up is complete (year 3-4 of the trial) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 124
Study Start Date: August 2014
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cyclophosphamide and BIBF-1120
Patients will receive oral BIBF 1120 (200mg bd) and cyclophosphamide (100mg) on a daily basis until disease progression or unacceptable toxicity.
Drug: BIBF 1120
Patients will receive either cyclophosphamide (100mg)and oral BIBF 1120 (200mg bd) or cyclophosphamide (100mg) and placebo.
Other Name: BIBF 1120 brand name: Nintedanib.
Placebo Comparator: Cyclophosphamide and placebo
Patients will receive oral BIBF 1120 (200mg bd) and placebo capsules on a daily basis until disease progression or unacceptable toxicity.
Drug: BIBF 1120
Patients will receive either cyclophosphamide (100mg)and oral BIBF 1120 (200mg bd) or cyclophosphamide (100mg) and placebo.
Other Name: BIBF 1120 brand name: Nintedanib.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female subjects, ≥18 years, histologically proven recurrent advanced 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
  • Performance status 0-2
  • Adequate organ function
  • Life expectancy > 6 weeks
  • Has received 2 or more lines of chemotherapy
  • No previous oral cyclophosphamide or Nintedanib, or other tyrosine kinase inhibitors but may have had VEGF inhibitors
  • At least 1 measurable lesion according to RECIST 1.1 criteria or any other baseline prerequisite
  • Declined any further standard IV chemotherapy
  • Able to give written informed consent and to complete QoL

Exclusion Criteria:

  • Malignant tumour of non-epithelial origin
  • Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture
  • Symptoms or signs of GI obstruction requiring parenteral nutrition or hydration or any other GI disorders or abnormalities that would interfere with drug absorption
  • Active brain metastases (i.e.stable for < 4weeks, symptoms deteriorating) or leptomeningeal disease. Trial entry is allowed if the brain metastases are stable. Dexamethasone is allowed if administered as stable dose for at least one month before randomisation
  • Clinically relevant therapy-related toxicity from previous chemotherapy and radiotherapy
  • History of major thromboembolic event, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation (aspirin <325 mg daily allowed as is low molecular weight heparin or warfarin)
  • Known inherited or acquired bleeding disorder
  • Significant cardiovascular diseases
  • 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:

    • creatinine >1.5 x ULN or 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 < 9.0 g/dL
    • proteinuria CTCAE 2 or greater
    • total bilirubin > x 2 ULN
    • ALT or AST > 1.5 x ULN unless liver metastases present when ALT / AST > 2.5 x ULN
    • International normalized ratio (INR) >2 or activated partial thromboplastin time (APPT) >1.5 x ULN in the absence of therapeutic anticoagulation. INR >4 or APTT >2.5 x ULN in presence of stable anticoagulation.
  • Serious infections in particular if requiring systemic antibiotic
  • Poorly controlled diabetes mellitus or patient on sulphonylurea-type hypoglycaemics (e.g. glicazide) as main diabetic control
  • Other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included:

    • non-melanomatous skin cancer (if adequately treated)
    • cervical carcinoma in situ (if adequately treated)
    • carcinoma of the breast (if adequately treated >5 years ago)
    • 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 that may increase the risk associated with study participation or study drug administration
  • Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
  • Any contraindications for therapy with cyclophosphamide
  • Chemotherapy, including immunotherapy or monoclonal antibody treatment (VEGF) within 4 weeks of study start. Hormones within 2 weeks of study start. Any previous tyrosine kinase inhibitor treatment or radiotherapy of measurable evaluable disease will make the patient ineligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610869

Contacts
Contact: Helen Christensen, Trial Coordinator 020 7679 9857 ctc.metrobibf@ucl.ac.uk

Locations
United Kingdom
Kent Oncology Centre Not yet recruiting
Maidstone, Kent, United Kingdom
Principal Investigator: Dr Jeff Summers         
Beatson West of Scotland Cancer Centre Not yet recruiting
Glasgow, Scotland, United Kingdom
Principal Investigator: Dr Rosalind Glasspool         
Velindre Hospital Not yet recruiting
Cardiff, Wales, United Kingdom
Principal Investigator: Dr Emma Hudson         
Royal United Hospital Not yet recruiting
Bath, United Kingdom
Principal Investigator: Dr Rebecca Bowen         
Addenbrookes Hospital Not yet recruiting
Cambridge, United Kingdom
Principal Investigator: Dr Helena Earl         
Royal Derby Hospital Not yet recruiting
Derby, United Kingdom
Principal Investigator: Dr Mojca Persic         
Mount Vernon Hospital Recruiting
Greater London, United Kingdom
Principal Investigator: Dr Marcia Hall         
Royal Surrey County Hospital Not yet recruiting
Guildford, United Kingdom
Principal Investigator: Dr Agnieszka Michael         
St James's University Hospital Not yet recruiting
Leeds, United Kingdom
Principal Investigator: Dr Alison Young         
Clatterbridge Centre for Oncology Not yet recruiting
Liverpool, United Kingdom
Principal Investigator: Dr Rosemary Lord         
University College London Hospital (UCLH) Not yet recruiting
London, United Kingdom
Principal Investigator: Prof Jonathan Ledermann         
Royal Marsden Hospital Recruiting
London, United Kingdom
Principal Investigator: Dr Susana Banerjee         
St Bartholomew's Hospital Not yet recruiting
London, United Kingdom
Principal Investigator: Dr Michelle Lockley         
Christie Hospital Not yet recruiting
Manchester, United Kingdom
Principal Investigator: Dr Andrew Clamp         
Churchill Hospital Not yet recruiting
Oxford, United Kingdom
Principal Investigator: Dr Shibani Nicum         
Wexham Park Hospital Recruiting
Slough, United Kingdom
Principal Investigator: Dr Marcia Hall         
Sponsors and Collaborators
University College, London
Boehringer Ingelheim
Investigators
Principal Investigator: Dr Marcia Hall Mount Vernon Cancer Centre
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01610869     History of Changes
Other Study ID Numbers: UCL/10/0470, 2011-005814-12
Study First Received: November 25, 2011
Last Updated: August 29, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by University College, London:
Recurrence
Ovarian Neoplasms
Ovarian Diseases
Fallopian Tube Neoplasms
Neoplasms
Carcinoma
Neoplasms by site

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Cyclophosphamide
Nintedanib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014