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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer Research UK
National Health and Medical Research Council, Australia
ANZGOG
NCIC Clinical Trials Group
Grupo Español de Investigación en Cáncer de Ovario
AstraZeneca
Information provided by (Responsible Party):
Andrew Embleton, Medical Research Council
ClinicalTrials.gov Identifier:
NCT00532194
First received: September 19, 2007
Last updated: September 21, 2015
Last verified: September 2015
  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 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, Placebo-controlled, Trial of Concurrent Cediranib [AZD2171] (With Platinum-based Chemotherapy) and Concurrent 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:
  • Progression-free survival [ Time Frame: Apr 2013 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Q2 2016 ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Q2 2015 ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: Q2 2015 ] [ Designated as safety issue: No ]

Enrollment: 486
Study Start Date: July 2007
Estimated Study Completion Date: December 2016
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A (reference)
Patients in this arm will receive standard platinum based chemotherapy plus a daily oral placebo tablet for the duration of chemotherapy and then until protocol defined disease progression occurs.
Active Comparator: B (concurrent cediranib)
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 until protocol defined disease progression occurs.
Drug: cediranib
Once-daily oral tablet starting dose 20mg
Other Names:
  • AZD2171
  • Recentin
Active Comparator: C (concurrent and maintenance cediranib)
Patients in this arm will receive standard platinum based chemotherapy plus a daily oral cediranib tablet during chemotherapy until protocol defined disease progression occurs.
Drug: cediranib
Once-daily oral tablet starting dose 20mg
Other Names:
  • AZD2171
  • Recentin

Detailed Description:

ICON6 is a randomised three-arm, two stage, double-blind, placebo-controlled multicentre Gynaecologic Cancer InterGroup (GCIG) phase III trial.

All patients will receive 6 cycles of platinum-based chemotherapy. Trial drug will be administered for up to 18 months from randomisation or until progression, whichever is sooner. Patients who have not progressed at 18 months from randomisation can continue Trial Drug until progression, if in the opinion of the clinician and the patient there is continuing clinical benefit.

Patients in Arm A (the reference arm) will receive a platinum-based chemotherapy regimen plus a daily oral placebo tablet for the duration of the chemotherapy and up to 18 months from randomisation or until progression.

Patients in Arm B (concurrent cediranib arm) will also receive a platinum-based chemotherapy regimen plus daily oral cediranib during chemotherapy only, and then an oral daily placebo tablet up to 18 months from randomisation or until progression.

Patients in Arm C (concurrent and maintenance cediranib arm) will also receive a platinum-based chemotherapy regimen plus oral cediranib daily during chemotherapy and then continued up to 18 months from randomisation or until progression.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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, Greater London, United Kingdom, WC1E 6BT
Sponsors and Collaborators
Medical Research Council
Cancer Research UK
National Health and Medical Research Council, Australia
ANZGOG
NCIC Clinical Trials Group
Grupo Español de Investigación en Cáncer de Ovario
AstraZeneca
Investigators
Principal Investigator: Jonathan Ledermann, Prof. University College, London
  More Information

Additional Information:
Publications:
Ledermann J, Perren T, Raja F, Embleton A, Rustin GJS, Jayson G, Kaye SB, Swart AM, Vaughan M, Hirte H. 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).

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrew Embleton, ICON6 Statistician, Medical Research Council
ClinicalTrials.gov Identifier: NCT00532194     History of Changes
Obsolete Identifiers: NCT00544973
Other Study ID Numbers: 2007-001346-41  ISRCTN68510403  2007-001346-41 
Study First Received: September 19, 2007
Last Updated: September 21, 2015
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
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Cediranib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2016