ICON8: Weekly Chemotherapy in Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by Medical Research Council
Sponsor:
Collaborator:
Clinical Trials Awards and Advisory Committee
Information provided by (Responsible Party):
Medical Research Council
ClinicalTrials.gov Identifier:
NCT01654146
First received: June 20, 2012
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to determine if weekly chemotherapy (i.e. giving paclitaxel or carboplatin at a lower dose every week) is more effective than standard chemotherapy (paclitaxel and carboplatin given once every three weeks over 18 weeks) in treating ovarian cancer. The investigators also want to see if weekly chemotherapy causes more or fewer side-effects than standard chemotherapy.


Condition Intervention Phase
Ovarian Cancer
Drug: Carboplatin
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An International Phase III Randomised Trial of Dose Fractionated Chemotherapy Compared to Standard Three Weekly Chemotherapy, Following Immediate Primary Surgery or as Part of Delayed Primary Surgery, for Women With Newly Diagnosed Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by Medical Research Council:

Primary Outcome Measures:
  • Stage 1: Feasibility assessed as the number of cycles and dose intensity of protocol treatment delivered per patient. [ Time Frame: 6 months after the 50th patient has been randomised to each arm and 6 months after the 50th patient with a plan to undergo delayed primary surgery has been randomised to each arm ] [ Designated as safety issue: No ]
  • Stage 1: Safety assessed as the rate of any ≥ grade 3 toxicity experienced per patient. [ Time Frame: 6 months after the 50th patient has been randomised to each arm and 6 months after the 50th patient with a plan to undergo delayed primary surgery has been randomised to each arm ] [ Designated as safety issue: Yes ]
  • Stage 2: Progression Free Survival rate at 9 months after randomisation [ Time Frame: 9 months after first 62 patients randomised per arm ] [ Designated as safety issue: No ]
  • Stage 3: Progression Free Survival [ Time Frame: PFS expected 1 year after last patient is randomised. OS expected 3 years after last patient is randomised. ] [ Designated as safety issue: No ]
  • Stage 3: Overall Survival [ Time Frame: PFS expected 1 year after last patient is randomised. OS expected 3 years after last patient is randomised. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Stage 3: Toxicity assessed by number of participants with adverse events [ Time Frame: Expected 1 year and 3 years after last patient is randomised. ] [ Designated as safety issue: No ]
    Assessment of toxicity profile of dose-fractionated chemotherapy

  • Stage 3: Quality of Life [ Time Frame: Expected 1 year and 3 years after last patient is randomised. ] [ Designated as safety issue: No ]
    Assessment of potential impact of dose-fractionated chemotherapy on functionality and well-being in patients undergoing first line treatment for ovarian cancer.

  • Stage 3: Health Economics [ Time Frame: Expected 1 year and 3 years after last patient is randomised. ] [ Designated as safety issue: No ]
    Cost-effectiveness analysis of dose-fractionated chemotherapy


Estimated Enrollment: 1485
Study Start Date: June 2011
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 (Control Arm)
Carboplatin and paclitaxel on day 1 of a 21-day cycle for 6 cycles
Drug: Carboplatin
AUC5 by intravenous infusion over 30-60 minutes
Drug: Paclitaxel
175mg/m2 by intravenous infusion over 3 hours
Experimental: Arm 2 (Research arm)
Carboplatin on day 1 and dose-fractionated weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles
Drug: Carboplatin
AUC5 by intravenous infusion over 30-60 minutes
Drug: Paclitaxel
80mg/m2 by intravenous infusion over 1 hour
Experimental: Arm 3 (Research arm)
Dose-fractionated weekly carboplatin and weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles.
Drug: Carboplatin
AUC2 by intravenous infusion over 30-60 minutes
Drug: Paclitaxel
80mg/m2 by intravenous infusion over 1 hour

Detailed Description:

ICON8 is a three-arm, three stage trial. Patients will be randomised in a 1:1:1 ratio. Patients in arm 1 (control arm) will receive weekly carboplatin and paclitaxel on day 1 of a 21-day cycle for 6 cycles. Patients in arm 2 will receive carboplatin on day 1 and dose-fractionated weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles. Patients in arm 3 will receive dose-fractionated weekly carboplatin and dose-fractionated weekly paclitaxel on day 1, 8 and 15 of a 21-day cycle for 6 cycles.

The trial will have three planned stages. Stage 1 will be conducted to confirm feasibility and safety of protocol treatment in all patients and separately in the Delayed Primary Surgery (DPS) patients. The outcome measure for stage 2 will be 9-month progression-free survival (PFS) rate. The primary outcome measures for stage 3 will be PFS and overall survival and secondary outcomes will be toxicity, Quality of Life and Health Economics. If pre-defined levels of deliverability, at stage 1, or activity, at stage 2, are not met then the research arms will be reconsidered.

  Eligibility

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

Inclusion Criteria:

  • Females aged 18 years or more
  • Signed informed consent and ability to comply with the protocol
  • Histologically confirmed, with core biopsy from a disease site as minimum requirement (cytology alone is insufficient for diagnosis):

    • Epithelial ovarian carcinoma
    • Primary peritoneal carcinoma of Müllerian histological type
    • Fallopian tube carcinoma
  • FIGO stage IC or above, which may be based on clinical and radiological assessment in patients who have not undergone immediate primary surgery
  • Confirmed high-risk histological subtype for patients with FIGO stage IC/IIA disease, namely:

    • High grade serous carcinoma
    • Clear cell carcinoma
    • Other histological subtype considered poorly differentiated/grade 3
  • ECOG Performance Status (PS) 0-2
  • Life expectancy > 12 weeks
  • 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)
  • Adequate liver function (within 28 days prior to randomisation):

    • Serum bilirubin (BR) ≤ 1.5 x ULN
    • Serum transaminases ≤ 3 x ULN in the absence of parenchymal liver metastases or ≤ 5 x ULN in the presence of parenchymal liver metastases
  • Adequate renal function as defined by GFR (Glomerular Filtration Rate) ≥ 30ml/min.

Exclusion Criteria:

  • Non-epithelial ovarian cancer, including malignant mixed Müllerian tumours (carcinosarcomas)
  • Peritoneal cancer that is not of Müllerian origin, including mucinous histology
  • Borderline tumours (tumours of low malignant potential)
  • Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
  • Previous malignancies within 5 years prior to randomisation apart from: adequately treated carcinoma in-situ of the cervix, breast ductal carcinoma in-situ, non-melanomatous skin cancer; or previous/synchronous early-stage endometrial cancer defined as stage IA (FIGO 2009) grade 1 or 2 endometrioid cancers with no lymphovascular space invasion
  • Pre-existing sensory or motor neuropathy grade ≥ 2
  • Evidence of any other disease/metabolic dysfunction that in the opinion of the investigator would put the subject at high-risk of treatment-related complications or prevent compliance with the trial protocol
  • Planned intraperitoneal cytotoxic chemotherapy
  • Any previous radiotherapy to the abdomen or pelvis
  • Sexually active women of childbearing potential not willing to use adequate contraception (e.g. oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least six months afterwards
  • Pregnant or lactating women
  • Treatment with any other investigational agent prior to protocol defined progression
  • Known hypersensitivity to carboplatin, paclitaxel or their excipients (including cremophor)
  • 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 brain or meningeal metastases are not eligible
  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: NCT01654146

Locations
United Kingdom
Medical Research Council Clinical Trials Unit Recruiting
London, United Kingdom, WC2B 6NH
Contact: Monique Tomiczek    02076704767    icon8@ctu.mrc.ac.uk   
Contact: Laura Farrelly    02076704789    icon8@ctu.mrc.ac.uk   
Sponsors and Collaborators
Medical Research Council
Clinical Trials Awards and Advisory Committee
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Research Council
ClinicalTrials.gov Identifier: NCT01654146     History of Changes
Other Study ID Numbers: 2010-022209-16, 10356387
Study First Received: June 20, 2012
Last Updated: July 26, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Medical Research Council:
Ovarian cancer
Epithelial ovarian carcinoma
Fallopian tube carcinoma
Primary serous peritoneal carcinoma
Gynaecological carcinoma
Randomised controlled trial

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014