['ovarian cancer', 'fallopian tube cancer']
['bibf 1120']

        Inclusion Criteria:

          -  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

          -  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

        Exclusion Criteria

          -  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:

               1. calculated GFR < 45 ml/min. Sites can use any calculation method according to
                  local practice.

               2. absolute neutrophil count (ANC) < 1.5x109/L

               3. platelets < 100 x109/L

               4. haemoglobin < 90 g/L

               5. proteinuria CTCAE 2 or greater

               6. total bilirubin > x 2 ULN

               7. ALT and/or AST > 1.5 x ULN

               8. unless liver metastases present when ALT or AST > 2.5 ULN

               9. 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:

               1. non-melanoma skin cancer (if adequately treated)

               2. cervical carcinoma in situ (if adequately treated)

               3. 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
      