An RCT of Concurrent and Maintenance Cediranib in Women With Platinum-sensitive Relapsed Ovarian Cancer (ICON6)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by Medical Research Council.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
ANZGOG
Clinical Trials Awards and Advisory Committee
AstraZeneca
NCIC Clinical Trials Group
Grupo Español de Investigación en Cáncer de Ovario
Information provided by (Responsible Party):
Medical Research Council
ClinicalTrials.gov Identifier:
NCT00532194
First received: September 19, 2007
Last updated: December 20, 2011
Last verified: December 2011
  Purpose

The purpose of this study is to assess the safety and efficacy of cediranib in combination with standard chemotherapy, in patients who have relapsed with ovarian, fallopian tube or epithelial cancer, after first line platinum based treatment.


Condition Intervention Phase
Ovarian Cancer
Drug: cediranib
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Trial of Concurrent (With Platinum Based Chemotherapy) and Maintenance Cediranib in Women With Platinum Sensitive Relapsed Ovarian Cancer.

Resource links provided by NLM:


Further study details as provided by Medical Research Council:

Primary Outcome Measures:
  • Stage 1: Safety [ Time Frame: Dec 2009 ] [ Designated as safety issue: Yes ]
  • Stage 2: Progression-free survival [ Time Frame: Dec 2012 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Stage 2: Overall survival, toxicity and Quality of Life [ Time Frame: Dec 2012 ] [ Designated as safety issue: No ]

Estimated Enrollment: 470
Study Start Date: October 2007
Estimated Study Completion Date: December 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Reference
Patients in this arm will receive standard platinum based chemotherapy plus a daily oral placebo tablet for the duration of chemotherapy and then for 18 months from the time of randomisation or until protocol defined disease progression occurs.
Drug: cediranib
once-daily oral tablet starting dose 20mg
Other Name: AZD2171 and recentin
Active Comparator: B
Patients in this arm will receive standard platinum based chemotherapy plus a daily oral cediranib tablet during chemotherapy only and then an oral daily placebo tablet for 18 months from the time of randomisation or until protocol defined disease progression occurs. 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
Drug: cediranib
once-daily oral tablet starting dose 20mg
Other Name: AZD2171 and recentin
Active Comparator: C
Patients in this arm will receive standard platinum based chemotherapy plus a daily oral cediranib tablet during chemotherapy and continued for 18 months from the time of randomisation or until protocol defined disease progression occurs. 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
Drug: cediranib
once-daily oral tablet starting dose 20mg
Other Name: AZD2171 and recentin

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 haemoptysis
  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 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
  20. Concomitant use of potent inhibitors of CYP3A4 and 2C8 which cannot be stopped without a 2 week washout period before starting Trial Drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532194

Locations
United Kingdom
University College London
London, United Kingdom, NW1
Sponsors and Collaborators
Medical Research Council
ANZGOG
Clinical Trials Awards and Advisory Committee
AstraZeneca
NCIC Clinical Trials Group
Grupo Español de Investigación en Cáncer de Ovario
Investigators
Principal Investigator: Jonathan Ledermann, Prof University College, London
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Research Council, ICON6 Trial Manager
ClinicalTrials.gov Identifier: NCT00532194     History of Changes
Obsolete Identifiers: NCT00544973
Other Study ID Numbers: 2007-001346-41, ISRCTN68510403
Study First Received: September 19, 2007
Last Updated: December 20, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Medical Research Council:
ovarian cancer
fallopian tube cancer
primary serous peritoneal cancer
gynaecological carcinoma
randomised controlled trial
Cediranib
AZD2171
efficacy

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Cediranib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014