ow dose cyclophosphamide +/- nintedanib in advanced ovarian cancer

Phase 1

• Conditions: Advanced ovarian cancer; MedDRA version: 18.0 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005814-12-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-07-02
• Study Completion: 2018-01-11
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 117

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

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 62

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 the patient is not eligible)
- Clinically relevant therapy-related toxicity from previous chemotherapy and radiotherapy
- History of major thromboembolic event within 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)
- 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 at baseline indicating an increased risk for adverse events:
a.calculated GFR < 45 ml/min. Sites can use any calculation method according to local practice.
b.absolute neutrophil count (ANC) <1.5 x 109/L
c.platelets <100 x 109/L
d.haemoglobin < 90 g/L
e.proteinuria CTCAE 2 or greater
f.total bilirubin higher than twice ULN
g.ALT and/or AST > 1.5 x ULN unless liver metastases present when ALT / AST > 2.5 ULN
h. International normalized ratio (INR)>2, prothrombin time (PT) and activated partial thromboplastin time (APPT) > 1.5 x ULN in the absence of therapeutic anticoagulation
- Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal or antiviral therapy), including active or chronic hepatitis B and/or C infection, HIV- infection
- Poorly controlled diabetes mellitus
- 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:
(a) non-melanoma skin cancer (if adequately treated)
(b) cervical carcinoma in situ (if adeq

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified