ICON8: Weekly Chemotherapy in Ovarian Cancer

Ovarian Cancer Clinical Trial

— ICON8  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01654146
• Other study ID #: 2010-022209-16
• Secondary ID: 10356387
• Status: Recruiting
• Phase: Phase 3
• First received: June 20, 2012
• Last updated: July 26, 2012
• Start date: June 2011

Study information

• Verified date: July 2012
• Source: Medical Research Council
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1485
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Carboplatin
AUC5 by intravenous infusion over 30-60 minutes
• Carboplatin
AUC2 by intravenous infusion over 30-60 minutes
• Paclitaxel
175mg/m2 by intravenous infusion over 3 hours
• Paclitaxel
80mg/m2 by intravenous infusion over 1 hour

Locations

Country	Name	City	State
United Kingdom	Medical Research Council Clinical Trials Unit	London

Sponsors (2)

Lead Sponsor	Collaborator
Medical Research Council	Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Feasibility assessed as the number of cycles and dose intensity of protocol treatment delivered per patient.		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	No
Primary	Stage 1: Safety assessed as the rate of any = grade 3 toxicity experienced per patient.		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	Yes
Primary	Stage 2: Progression Free Survival rate at 9 months after randomisation		9 months after first 62 patients randomised per arm	No
Primary	Stage 3: Progression Free Survival		PFS expected 1 year after last patient is randomised. OS expected 3 years after last patient is randomised.	No
Primary	Stage 3: Overall Survival		PFS expected 1 year after last patient is randomised. OS expected 3 years after last patient is randomised.	No
Secondary	Stage 3: Toxicity assessed by number of participants with adverse events	Assessment of toxicity profile of dose-fractionated chemotherapy	Expected 1 year and 3 years after last patient is randomised.	No
Secondary	Stage 3: Quality of Life	Assessment of potential impact of dose-fractionated chemotherapy on functionality and well-being in patients undergoing first line treatment for ovarian cancer.	Expected 1 year and 3 years after last patient is randomised.	No
Secondary	Stage 3: Health Economics	Cost-effectiveness analysis of dose-fractionated chemotherapy	Expected 1 year and 3 years after last patient is randomised.	No

External Links

•   ICON8 Trial website