ICON8 Trials ProgrammeICON8: Weekly chemotherapy in ovarian cancer, andICON8B: Weekly chemotherapy and bevacizumab in advanced ovarian cancer
- Conditions
- ICON8: Newly diagnosed high risk early stage (FIGO stage IC/IIA, grade 3 or clear cell histology only) or advanced stage (FIGO stage IIB-IV,all grades and all histological types) epithelial ovarian, fallopian tube or primary peritoneal carcinoma.ICON8B: Patients with newly diagnosed, histologically confirmed high-risk stage III-IV ovarian cancer: FIGO (2013) stage IIIA-C disease with >1cm residual disease following IPS or those planned to undergo primary chemotherapy with or without DPS.MedDRA version: 21.0Level: LLTClassification code 10016183Term: Fallopian tube cancer NOSSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10033159Term: Ovarian epithelial cancer NOSSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10052171Term: Peritoneal carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-022209-16-IE
- Lead Sponsor
- niversity College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 2655
ICON8 Inclusion Criteria:
1. Females aged 18 years and above
2. Signed informed consent and ability to comply with the protocol
3. 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
• Ovarian carcinosarcoma (malignant mixed Müllerian tumour (MMMT) of the ovary)
4. FIGO stage IC or above, which may be based on clinical and radiological assessment in patients who have not undergone immediate primary surgery
5. 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
6. ECOG Performance Status (PS) 0-2
7. Life expectancy > 12 weeks
8. Adequate bone marrow function
• Absolute Neutrophil Count >1.5 x 10^9/l
• Platelets (Plt) >100 x 10^9/l
• Haemoglobin (Hb) > 9g/dl (can be post transfusion)
9. Adequate liver function (within 28 days prior to randomisation)
• Serum bilirubin = 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
10. Adequate renal function as defined by:
• Directly measured GFR (Glomerular Filtration Rate) = 30 ml/min, or
• Calculated creatinine clearance = 60 ml/min
NB. If the calculated creatinine clearance is <60 ml/min the GFR should be directly measured using either a 24 hour urine collection or an isotopic evaluation
11. Able to start chemotherapy within 8 weeks after immediate primary surgery (where applicable)
ICON8B Inclusion Criteria:
1. Females aged 18 years or above
2. Signed informed consent and ability to comply with the protocol
3. 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
• Ovarian carcinosarcoma (malignant mixed Müllerian tumour (MMMT) of the ovary)
4. High –risk disease defined as
• FIGO (2013) Stage IIA1(ii), IIA2 with positive retroperitoneal lymph nodes >10mm in diameter, IIIB or IIIC disease
i. With >1cm residual disease following IPS or
ii. Planned to undergo primary chemotherapy with or without DPS
• FIGO Stage IV disease:
i. With any volume of residual disease following IPS or
ii. Planned to undergo primary chemotherapy with or without DPS
5. ECOG Performance Status (PS) 0-2
6. Life expectancy >12 weeks
7. Adequate bone marrow function;
• Absolute Neutrophil Count (ANC) = 1.5 x 10^9/l
• Platelets (Plt) =100 x 10^9/l
• Haemoglobin (Hb) =9g/dl (can be post transfusion)
8. Adequate liver function;
• 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
9. Adequate renal function as defined by:
• Directly measured GFR (Glomerular Filtration Rate) =30 ml/min, or
• Calculated creatinine clearance =60ml/min
NB. If the calculated creatinine clearance is <60 ml/min the GFR should be directly measured using either a 24 hour urine collection or an isotopic evaluation
10. Adequate coagulation profile:
• International normalised ratio (INR) =1.5
• Activated prothrombin time (APTT) =
ICON8 Exclusion Criteria;
1. Non-epithelial ovarian cancer
2. Peritoneal cancer that is not of Müllerian origin, including mucinous histology
3. Borderline tumours (tumours of low malignant potential)
4. Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
5. 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
6. Pre-existing sensory or motor neuropathy grade =2
7. 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
8. Planned intraperitoneal cytotoxic chemotherapy
9. Planned maintenance treatment with systemic anti-cancer therapy following completion of protocol treatment and prior to protocol defined progression
10. Any previous radiotherapy to the abdomen or pelvis
11. Sexually active women of childbearing potential not willing to use adequate contraception (eg. 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
12. Pregnant or lactating women who are currently breastfeeding
13. Treatment with any other investigational agent prior to protocol defined progression
14. Known hypersensitivity to carboplatin, paclitaxel or their excipients (including cremophor)
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 brain or meningeal metastases are not eligible.
Additional Exclusion Criteria for ICON8B:
1. Proteinuria at baseline:
• >1gm protein/24h by a 24-hour urine collection
NB. Proteinuria should be initially assessed by urine dipstick. If urine protein is =2+ on urine dipstick, a 24-hour urine protein collection must be performed.
2. Significant co-existing or previous medical conditions that are contra-indications to treatment with bevacizumab, including;
a. Cerebrovascular disease, including transient ischaemic attacks (TIAs), cerebrovascular accident (CVA; i.e. stroke) and intracranial bleeds (i.e. intra-cerebral haemorrhage, sub-arachnoid haemorrhage or sub-dural haemorrhage) within 6 months before trial entry
b. Cardiovascular disease as follows:
i. Uncontrolled hypertension, defined as sustained BP>150/100mgHg while receiving anti-hypertensive medication
ii. Myocardial infarction or unstable angina within 6 months prior to randomisation
iii. New York Heart Association (NYHA) grade =2 congestive heart failure
iv. Poorly controlled cardiac arrhythmia despite medication
NB. Patients with rate-controlled atrial fibrillation are eligible
v. Peripheral vascular disease grade =3, i.e. symptomatic and interfering with activities of daily living requiring repair or revision
c. History or evidence of bleeding diathesis or coagulopathy (in patients not on therapeutic anti-coagulant medication)
d. Recent history of proven
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method