Know Cancer

forgot password

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

Phase 2
18 Years
Not Enrolling
Ovarian Cancer, Fallopian Tube Cancer

Thank you

Trial Information

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

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

Inclusion Criteria:

- Female subjects, >18 years, histologically proven recurrent advanced ovarian,
fallopian tube or primary peritoneal carcinomas

- 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

- 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

- 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

- Clinically relevant therapy-related toxicity from previous chemotherapy and

- History of major thromboembolic event, such as pulmonary embolism or proximal deep
vein thrombosis, unless on stable therapeutic anticoagulation (aspirin <325mg daily
allowed as is low dose heparin for maintenance of in-dwelling venous catheter)

- 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 >

- total bilirubin > x 2 ULN

- ALT or AST > 1.5 x ULN unless liver metastases present when ALT / AST > 2.5 ULN

- International normalized ratio (INR)>2, prothrombin time (PT) and activated
partial thromboplastin time (APPT) > 50% of deviation of institutional ULN in
the absence of therapeutic anticoagulation

- Serious infections in particular if requiring systemic antibiotic

- Poorly controlled diabetes mellitus

- 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

- Women of childbearing potential who are sexually active and not using a highly
effective method of birth control during the trial and for at least 3 months after
the end of active therapy

- Pregnancy and breastfeeding, female patients of childbearing potential must have a
negative pregnancy test prior to commencing study treatment.

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival

Outcome Description:

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

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

Dr Marcia Hall

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mount Vernon Cancer Centre


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

September 2012

Completion Date:

September 2015

Related Keywords:

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Recurrence
  • Ovarian Neoplasms
  • Ovarian Diseases
  • Fallopian Tube Neoplasms
  • Neoplasms
  • Carcinoma
  • Neoplasms by site
  • Ovarian Neoplasms
  • Fallopian Tube Neoplasms