A trial looking at cediranib for ovarian cancer that has come back (ICON6) | Not Recruiting
A trial looking at cediranib for ovarian cancer that has come back (ICON6)
ICON6 (International Collaborative Ovarian Neoplasm 6)
Trial Source

Health Conditions
  • Relapsed platinum-sensitive ovarian cancer
Not Recruiting
Recruitment Status
ISRCTN68510403
Primary Trial ID Number
Summary
Current hypothesis as of 13/03/2015: That cediranib has an influence on progression-free survival when comparing patients receiving chemotherapy alone with patients receiving chemotherapy and cediranib (AZD2171). Previous hypothesis: Over three separate trial stages the study hypotheses are: Stage 1: That it is safe to add a once daily tablet of cediranib to standard platinum-based chemotherapy Stage 2: That cediranib has an influence on progression free survival when comparing patients receiving chemotherapy alone with patients receiving chemotherapy and cediranib (AZD2171) Stage 3: 1. That cediranib has an effect on overall survival when taken at the same time as chemotherapy (placebo versus active), and when taken at the same time and then continued as a maintenance treatment (placebo versus active) 2. If the first Stage 3 assessments shows the product is effective, that cediranib has an effect on overall survival when taken at the same time as chemotherapy compared with at the same time and then continued as a maintenance treatment On 13/03/2015 the following changes were made to the trial record: 1. The study design was changed from 'Randomised three-arm three-stage double-blind placebo-controlled multicentre phase III trial' to 'Randomised three-arm double-blind placebo-controlled multicentre phase III trial' 2. The overall trial end date was changed from 31/07/2013 to 31/12/2016. 3. The target number of participants was changed from 2000 to 470. 4. Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Norway, Serbia and Sweden were removed from the countries of recruitment. 5. Medical Research Council (UK) and NHMRC (Cancer Australia) were added as funders.
Primary Outcome Measures
  • Current primary outcome measures as of 13/03/2015:
  • Progression-free survival (PFS) in arms A vs C
  • Previous primary outcome measures:
  • Stage 1: Safety
  • Stage 2: Progression free survival
  • Stage 3: Overall survival
  • Data for the outcomes above will be collected approximately 3 weekly during chemotherapy, 6 weekly after chemotherapy up to 18 months, 3 monthly up to 3 years, 6 monthly during years 4 and 5, then annually until protocol defined disease progression or death.
Secondary Outcome Measures
  • Current secondary outcome measures as of 13/03/2015:
  • 1. Progression-free survival (PFS) across arms A, B and C
  • 2. Overall survival (OS)
  • 3. Toxicity
  • 4. Quality of Life (QoL)
  • Previous secondary outcome measures:
  • Stage 1: None
  • Stage 2: Overall survival and toxicity
  • Stage 3: Progression free survival, toxicity and quality of life
  • Quality of life assessment will be made using EORTC QLQ-C30 version 3 and EORTC QLQ-OV28. This information will be supplemented by health questionnaire EQ-5D. Other outcome measures will be assessed by clinical interview, blood tests and CT scans.
  • Data for the outcomes above will be collected approximately 3 weekly during chemotherapy, 6 weekly after chemotherapy up to 18 months, 3 monthly up to 3 years, 6 monthly during years 4 and 5, then annually until protocol defined disease progression or death.
Research Question
  • Current hypothesis as of 13/03/2015: That cediranib has an influence on progression-free survival when comparing patients receiving chemotherapy alone with patients receiving chemotherapy and cediranib (AZD2171). Previous hypothesis: Over three separate trial stages the study hypotheses are: Stage 1: That it is safe to add a once daily tablet of cediranib to standard platinum-based chemotherapy Stage 2: That cediranib has an influence on progression free survival when comparing patients receiving chemotherapy alone with patients receiving chemotherapy and cediranib (AZD2171) Stage 3: 1. That cediranib has an effect on overall survival when taken at the same time as chemotherapy (placebo versus active), and when taken at the same time and then continued as a maintenance treatment (placebo versus active) 2. If the first Stage 3 assessments shows the product is effective, that cediranib has an effect on overall survival when taken at the same time as chemotherapy compared with at the same time and then continued as a maintenance treatment On 13/03/2015 the following changes were made to the trial record: 1. The study design was changed from 'Randomised three-arm three-stage double-blind placebo-controlled multicentre phase III trial' to 'Randomised three-arm double-blind placebo-controlled multicentre phase III trial' 2. The overall trial end date was changed from 31/07/2013 to 31/12/2016. 3. The target number of participants was changed from 2000 to 470. 4. Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Norway, Serbia and Sweden were removed from the countries of recruitment. 5. Medical Research Council (UK) and NHMRC (Cancer Australia) were added as funders.
Design Type
Sorry, this information is not available
Ethics Approval
Oxfordshire Research Ethics Committee B, 16/07/2007, ref: 07/H0605/76
Publications
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21878941 2013 results in: Ledermann J, Perren T, Raja F, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: Results of the ICON6 trial. Eur J Cancer 2013;49(Suppl. 3):S5 (LBA10).
Countries of Recruitment
Australia; Canada; New Zealand; Spain; United Kingdom
Participant Sex
Female
Participant Age Range
Adult
Participant Type
Patient
Trial Sample Size
470
Participant Inclusion Criteria
  • 1. Females aged 18 years or older with previous histologically proven diagnosis of:
  • 1.1. Epithelial ovarian carcinoma
  • 1.2. Fallopian tube carcinoma
  • 1.3. Primary serous peritoneal carcinoma
  • Relapsing more than 6 months after completion of first-line platinum-based chemotherapy
  • 2. Signed informed consent and ability to comply with the protocol
  • 3. Ability to commence treatment within 2 weeks of randomisation
  • 4. Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) proven relapsed disease, more than six months since completion of first-line platinum-based chemotherapy
  • 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • 6. Life expectancy more than 12 weeks
  • 7. If there is a past history of a solid tumour, this must have been treated curatively more than five years ago with no evidence of recurrence
  • 8. Adequate bone marrow function
  • 8.1. Absolute Neutrophil Count (ANC) greater than or equal to 1.5 x 109/l
  • 8.2. Platelets (Plt) greater than or equal to 100 x 109/l
  • 8.3. Haemoglobin (Hb) greater than or equal to 9g/dl (can be post transfusion)
  • 9. Adequate liver function (within 14 days before randomisation)
  • 9.1. Serum bilirubin (BR) = 1.5 x Upper Limit of Normal (ULN)
  • 9.2. Serum transaminases = 2.5 x ULN
  • 10. Adequate renal function
  • 10.1. Serum creatinine = 1.5 ULN
  • 10.2. Urine dipstick for proteinuria less than 2+. If urine dipstick is greater than or equal to 2+ on two occasions more than one week apart then a 24 hour urine must demonstrate less than or equal to 1 g of protein in 24 hours
Participant Exclusion Criteria
  • 1. Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneum
  • 2. Poorly controlled hypertension (persistently elevated >150/100 mmHg 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 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 randomisation
  • 6. Treatment with any other investigational agent within 30 days 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 30 days 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. Gastrointestinal (GI) impairment that could affect ability to take, or adsorption of, oral medicines including sub acute or complete bowel obstruction
  • 9. Known hypersensitivity to AZD2171 or other Vascular Endothelial Growth Factor (VEGF) inhibitors
  • 10. Major surgery within 2 weeks before entry into the trial
  • 11. Significant haemorrhage of >30 ml in a single episode within 3 months or any haemoptysis
  • 12. Evidence of severe or uncontrolled cardiac disease
  • 12.1. Myocardial Infarct (MI) or unstable angina within 12 months
  • 12.2. New York Health Association (NYHA) = grade 2 Congestive Heart Failure (CHF)
  • 12.3. Cardiac ventricular arrhythmias requiring medication
  • 12.4. History of 2nd or 3rd degree atrioventricular conduction defects
  • 13. Prolonged QTc (corrected) interval of >470 msec on electrocardiogram (ECG), or a family history of long QT syndrome
  • 14. Persisting = Grade 2 CTC (Common Toxicity Criteria) 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 physician
  • 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
Interventions
Current interventions as of 13/03/2015: Patients in Arm A (the reference arm) will receive standard platinum-based chemotherapy plus a daily oral placebo tablet for the duration of the chemotherapy and then until protocol defined disease progression occurs. Patients in Arm B (concurrent cediranib arm) will also receive standard chemotherapy plus daily oral cediranib during chemotherapy only, and then an oral daily placebo tablet until protocol defined disease progression or toxicity limiting treatment occurs. Patients in Arm C (concurrent and maintenance cediranib arm) will also receive standard chemotherapy plus oral cediranib daily during chemotherapy and until protocol defined disease progression or toxicity limiting treatment occurs. Previous interventions: Patients in Arm A (the reference arm) will receive standard platinum-based chemotherapy plus a daily oral placebo tablet for the duration of the chemotherapy and then for up to 18 months from the time of randomisation, or until protocol defined disease progression occurs. Patients in Arm B (concurrent cediranib arm) will also receive standard chemotherapy plus daily oral cediranib during chemotherapy only, and then an oral daily placebo tablet for up to 18 months from the time of randomisation, or until protocol defined disease progression or toxicity limiting treatment occurs. Patients in Arm C (concurrent and maintenance cediranib arm) will also receive standard chemotherapy plus oral cediranib daily during chemotherapy and then continued for up to 18 months from the time of randomisation, or until protocol defined disease progression or toxicity limiting treatment occurs. The starting dose of cediranib is 30 mg taken orally once daily. This will be down titrated if required on medical assessment to 20 mg and then 15 mg.
Design Details
Sorry, this information is not available
Study Design
Randomised three-arm double-blind placebo-controlled multicentre phase III trial
Results Reporting
Sorry, this information is not available
Acronym
ICON6 (International Collaborative Ovarian Neoplasm 6)
Scientific Title
A double-blind, placebo-controlled, three-arm, randomised, multi-centre Gynaecologic Cancer InterGroup trial of cediranib (AZD2171), in combination with platinum-based chemotherapy and as a single agent maintenance therapy, in women with ovarian cancer relapsing more than 6 months following completion of first-line platinum-based treatment
Secondary Trial Identifying Number
N/A
Website
http://www.icon6.org/
Study Funded By
Cancer Research UK (ref: C444/A6862)
Funder Type
Sorry, this information is not available
Study Sponsored By
Medical Research Council (UK)
Study Also Sponsored By
Sorry, this information is not available
Primary Sponsor Type
Sorry, this information is not available
Secondary Sponsor Type
Sorry, this information is not available
Key Dates

Date of First Enrollment

29 Nov 2007

Recruitment End Date

23 Dec 2011

Trial End Date

31 Dec 2016

Date added to Registry

13 Aug 2007

Last Updated

02 Apr 2015