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A Randomised Trial of Concurrent (With Platinum Based Chemotherapy) and Maintenance Cediranib in Women With Platinum Sensitive Relapsed Ovarian Cancer.

Phase 2/Phase 3
18 Years
Open (Enrolling)
Ovarian Cancer

Thank you

Trial Information

A Randomised Trial of Concurrent (With Platinum Based Chemotherapy) and Maintenance Cediranib in Women With Platinum Sensitive Relapsed Ovarian Cancer.

The trial will be multi-arm and multi-stage. Patients will be randomised in a 2:3:3 ration
to arms A, B and C. Patients in arm A (reference arm) will receive standard 6 X 3 week
cycles of carboplatin and paclitaxel plus an oral placebo tablet they will take every day.
At the end of chemo they will continue to take a placebo tablet every day for 18 months from
randomisation or until progression. Patients in Arm B (concurrent arm) will get standard 6
cycles of chemo and take an oral daily cediranib tablet during chemo and then switch to take
a daily placebo tablet for 18 months from randomisation or until progression. Patients in
arm C (concurrent and maintenance arm) will get standard chemo plus oral daily cediranib
tablet during chemo and oral daily cediranib tablet for 18 months from randomisation or
until progression. This will allow us to see if there is an added benefit of taking
cediranib for a longer time after chemo has ended. Patients who have not progressed at 18
months from randomisation can continue trial drug until progression, if in the opinion of
the clinician there is a continuing clinical benefit.

The trial will be conducted in 2 stages. The first stage was conducted in selected centres
only in Canada and the UK to confirm the safety of using cediranib. The second stage was
conducted in centres in Australia, Canada, Spain and the UK. Stage 2 analysis will be
conducted following 1 year of follow up after approximately 470 patients have been
randomised. Stage 2 will assess whether a minimal level of efficacy is shown on progression
free survival. The trial will also look at quality of life, toxicity and have translational
research components.

Inclusion Criteria:

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

Exclusion Criteria:

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
12 months.

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
QT syndrome.

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.

Type of Study:


Study Design:

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

Outcome Measure:

Stage 1: Safety

Outcome Time Frame:

Dec 2009

Safety Issue:


Principal Investigator

Jonathan Ledermann, Prof

Investigator Role:

Principal Investigator

Investigator Affiliation:

University College, London


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

October 2007

Completion Date:

December 2012

Related Keywords:

  • Ovarian Cancer
  • ovarian cancer
  • fallopian tube cancer
  • primary serous peritoneal cancer
  • gynaecological carcinoma
  • randomised controlled trial
  • Cediranib
  • AZD2171
  • efficacy
  • Ovarian Neoplasms