A Randomised Trial of Concurrent (With Platinum Based Chemotherapy) and Maintenance Cediranib in Women With Platinum Sensitive Relapsed Ovarian Cancer.
1. Females aged >= 18 years with previous histologically proven diagnosis of
- Epithelial ovarian carcinoma
- Fallopian tube carcinoma
- Primary serous peritoneal carcinoma requiring treatment with further
platinum-based chemotherapy > 6 months after their last cycle of first-line
chemotherapy and 6 weeks after maintenance that is not chemotherapy based.
2. Signed informed consent and ability to comply with the protocol
3. Ability to commence treatment within approximately 2 weeks of randomisation
4. CT or MRI proven relapsed disease (measurable or non-measurable)
5. ECOG performance status 0-1
6. Life expectancy more than 12 weeks
7. If there is a past history of a solid tumour (other than ovarian cancer), this must
have been treated curatively more than five years ago with no evidence of recurrence,
with the exception of patients who have synchronous endometrial cancer (stage I G1,
G2) with their ovarian cancer
8. If prior anthracycline or chest radiotherapy, Left Ventricular Ejection Fraction
(LVEF) > institutional lower limit of normal.
9. Adequate bone marrow function
- Absolute Neutrophil Count (ANC) >= 1.5 x 109/l
- Platelets (Plt) >= 100 x 109/l
- Haemoglobin (Hb) >= 9g/dl (can be post transfusion)
10. Adequate liver function (within 14 days before randomisation)
- Serum bilirubin (BR) ≤ 1.5 x ULN
- Serum transaminases ≤ 2.5 x ULN
11. Adequate renal function
- Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance > 50 ml/min
- Urine dipstick for proteinuria <2+. If urine dipstick is >= 2+ on two occasions
more than one week apart then a 24 hour urine must demonstrate <=1g of protein
in 24 hours or protein/creatinine ratio <1.5
1. Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and
mucinous carcinoma of the peritoneum
2. Poorly controlled hypertension (persistently elevated > 150/100mmHg, either systolic
or diastolic or both, despite anti-hypertensive medication)
3. History of inflammatory bowel disease (Crohn's disease or Ulcerative Colitis)
4. Malignancies other than ovarian cancer within 5 years prior to randomisation, except
for synchronous endometrial cancer (Stage I G1,G2) with ovarian cancer,adequately
treated carcinoma in situ of the cervix and/or basal cell skin cancer. Patients who
have a past history of a solid tumour, treated curatively, more than five years prior
to randomisation, with no evidence of recurrence, are still eligible to enter ICON6.
5. Previous radiotherapy within 21 days prior to anticipated start of treatment
6. Treatment with any other investigational agent within 6 weeks prior to entering this
trial. Patients are still eligible for entry into ICON6 if they have received
previous treatment for ovarian cancer with either bevacizumab, erlotinib, or a Cox-2
inhibitor as long as more than 6 weeks have elapsed since the last treatment.
7. Arterial thrombotic event (including transient ischaemic attack [TIA],
cerebrovascular accident [CVA) and peripheral arterial embolus) within the previous
8. GI impairment that could affect ability to take, or adsorption of, oral medicines
including sub acute or complete bowel obstruction
9. Known hypersensitivity to cediranib or other VEGF inhibitors
10. Major surgery within 2 weeks before anticipated start of treatment
11. Significant haemorrhage of > 30ml in a single episode within 3 months or any
12. Evidence of severe or uncontrolled cardiac disease
- Myocardial infarct [MI] or unstable angina within 12 months
- New York Health Association (NYHA) ≥ grade 2 congestive heart failure (CHF)
- Cardiac ventricular arrhythmias requiring medication.
- History of 2nd or 3rd degree atrioventricular conduction defects.
13. Prolonged QTc (corrected) interval of > 470msec on ECG, or a family history of long
14. Persisting ≥ Grade 2 CTC toxicity (except alopecia and neuropathy) from previous
anti-cancer treatment. If peripheral sensory or motor neuropathy ≥ grade 2 then
paclitaxel can be omitted from the chemotherapy at the discretion of the treating
15. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI
of the brain is mandatory in the case of suspected brain metastases. Spinal MRI is
mandatory in the case of suspected spinal cord compression. Patients with unstable,
untreated brain or meningeal metastases are not eligible.
16. Inability to attend or comply with treatment or follow-up scheduling
17. Evidence of any other disease, metabolic dysfunction, physical examination finding or
laboratory finding giving reasonable suspicion of a disease or condition that
contra-indicates the use of an investigational drug or puts the patient at high risk
for treatment-related complications
18. Fertile women of childbearing potential not willing to use adequate contraception for
the duration of trial treatment and at least 6 months after.
19. Any other severe uncontrolled medical condition or disease
20. Concomitant use of potent inhibitors of CYP3A4 and 2C8 which cannot be stopped
without a 2 week washout period before starting Trial Drug.